ID Accession_number Authors Gene Gene_ID Antisense_21mer Sense_19mer 5.end 3' end Sec.dG Hsieh Amarzguioui GC stretch Whole ∆G Katoh Takasaki Reynolds Ui-Tei %GC i-score %Inhibition Technology Cell Concentration Hours Title PMID Year Abstract Journal Pubdate Si0001 NM_012249 Huesken TC10 23433 CUAAUAUGUUAAUUGAUUUau AAAUCAAUUAACAUAUUAG -0.9 -2.1 2.1 0 -1 1 -24.6 95.4 -1.3 6 II 15.8 57 46.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0002 NM_012249 Huesken TC10 23433 AAUAUGUUAAUUGAUUUAUac AUAAAUCAAUUAACAUAUU -1.1 -0.9 2.5 2 1 1 -23.6 104.2 -1 9 II 10.5 65.3 38.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0003 NM_012249 Huesken TC10 23433 GAUUUAUACAAUUCCUUUCaa GAAAGGAAUUGUAUAAAUC -2.4 -2.4 2.3 2 1 2 -28.2 102.6 12.7 7 II 26.3 61.5 51.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0004 NM_012249 Huesken TC10 23433 CAAUUCCUUUCAAUUUUAUcu AUAAAAUUGAAAGGAAUUG -1.1 -2.1 1.3 -1 -1 2 -26.2 87.4 -8.6 5 II 21.1 44.5 36.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0005 NM_012249 Huesken TC10 23433 CAGACCAAAAUUAAAUAAGaa CUUAUUUAAUUUUGGUCUG -2.1 -2.1 2.8 -1 -1 2 -27.4 79.6 -1.6 4 II 26.3 56.4 52.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0006 NM_012249 Huesken TC10 23433 AGACCAAAAUUAAAUAAGAaa UCUUAUUUAAUUUUGGUCU -2.4 -2.1 2.8 2 0 2 -27.7 65.6 -6.3 4 II 21.1 51.3 44.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0007 NM_012249 Huesken TC10 23433 ACCAAAAUUAAAUAAGAAAgu UUUCUUAUUUAAUUUUGGU -0.9 -2.2 2.8 1 -2 2 -25 79.6 1.3 6 II 15.8 48.6 44.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0008 NM_012249 Huesken TC10 23433 CAAAAUUAAAUAAGAAAGUua ACUUUCUUAUUUAAUUUUG -2.2 -2.1 3.7 -1 -1 1 -23.8 77.8 -5.9 6 II 15.8 59.3 43.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0009 NM_012249 Huesken TC10 23433 UAAGAAAGUUACAUAAGAUuc AUCUUAUGUAACUUUCUUA -1.1 -1.3 3.5 0 3 1 -28.2 78.1 -1.6 7 II 21.1 64.2 59.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0010 NM_012249 Huesken TC10 23433 AAGUUACAUAAGAUUCCAUuu AUGGAAUCUUAUGUAACUU -1.1 -0.9 2.3 1 2 2 -30.4 81.9 -1.9 6 II 26.3 54.2 51.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0011 NM_012249 Huesken TC10 23433 ACAUAAGAUUCCAUUUGAGca CUCAAAUGGAAUCUUAUGU -2.1 -2.2 1.4 1 4 2 -31.4 68.1 -2.3 6 Ia 31.6 52 55.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0012 NM_012249 Huesken TC10 23433 AAGAUUCCAUUUGAGCAUAca UAUGCUCAAAUGGAAUCUU -1.3 -0.9 1.4 1 -1 2 -32.6 71.6 -0.7 5 II 31.6 50.8 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0013 NM_012249 Huesken TC10 23433 CCAUUUGAGCAUACAUAAGgc CUUAUGUAUGCUCAAAUGG -2.1 -3.3 1.2 0 -1 2 -32.5 69 0.7 4 II 36.8 46 44 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0014 NM_012249 Huesken TC10 23433 CAUUUGAGCAUACAUAAGGcc CCUUAUGUAUGCUCAAAUG -3.3 -2.1 1.2 0 1 2 -32.5 74.1 0.4 6 II 36.8 63.2 65.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0015 NM_012249 Huesken TC10 23433 AUAAGGCCAUGAUACUUUAau UAAAGUAUCAUGGCCUUAU -1.3 -1.1 1.3 1 0 4 -32.9 70.1 -3.8 6 II 31.6 51.7 75.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0016 NM_012249 Huesken TC10 23433 GCCAUGAUACUUUAAUGUGaa CACAUUAAAGUAUCAUGGC -2.1 -3.4 1.2 0 0 3 -32.6 69 3 3 II 36.8 45.2 62.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0017 NM_012249 Huesken TC10 23433 UUAAUGUGAACCACCAUUUcu AAAUGGUGGUUCACAUUAA -0.9 -0.9 -2.4 1 1 2 -32 85.4 -11.3 9 II 31.6 76.4 85.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0018 NM_012249 Huesken TC10 23433 UGUGAACCACCAUUUCUUGga CAAGAAAUGGUGGUUCACA -2.1 -2.1 -0.3 0 3 2 -35.3 70.6 2.7 6 Ib 42.1 58.9 84.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0019 NM_012249 Huesken TC10 23433 GAACCACCAUUUCUUGGAAga UUCCAAGAAAUGGUGGUUC -0.9 -2.4 -0.8 1 0 2 -35.5 58.4 4 2 III 42.1 27 38.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0020 NM_012249 Huesken TC10 23433 AUUUCUUGGAAGAAAGAAGac CUUCUUUCUUCCAAGAAAU -2.1 -1.1 -1.4 3 3 2 -30.8 85.3 -0.3 6 Ia 31.6 66.7 53.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0021 NM_012249 Huesken TC10 23433 UGGAAGAAAGAAGACAUCCaa GGAUGUCUUCUUUCUUCCA -3.3 -2.1 -1.8 0 2 2 -36 64.9 12.4 6 Ib 42.1 74.2 83.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0022 NM_012249 Huesken TC10 23433 GGAAGAAAGAAGACAUCCAaa UGGAUGUCUUCUUUCUUCC -2.1 -3.3 -0.1 1 -1 2 -36 50.5 -4 4 II 42.1 40.7 68.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0023 NM_012249 Huesken TC10 23433 GAAAGAAGACAUCCAAAUGuc CAUUUGGAUGUCUUCUUUC -2.1 -2.4 0.2 0 1 2 -32.3 66.7 7.7 4 II 36.8 50.6 73.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0024 NM_012249 Huesken TC10 23433 AAGACAUCCAAAUGUCCGAuu UCGGACAUUUGGAUGUCUU -2.4 -0.9 -4.7 2 1 3 -36.3 68.9 -1.5 5 II 42.1 53.8 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0025 NM_012249 Huesken TC10 23433 CAUCCAAAUGUCCGAUUCAga UGAAUCGGACAUUUGGAUG -2.1 -2.1 0.8 -1 -2 3 -35.2 54.7 -5.7 4 II 42.1 41.2 38.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0026 NM_012249 Huesken TC10 23433 UUCCUGGCCAGUCAUCCAGua CUGGAUGACUGGCCAGGAA -2.1 -0.9 -4.5 2 3 4 -42.7 63.9 5.4 5 II 57.9 65.3 75.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0027 NM_012249 Huesken TC10 23433 CCUGGCCAGUCAUCCAGUAga UACUGGAUGACUGGCCAGG -1.3 -3.3 -5 0 -3 4 -42.9 34.8 -8.1 -1 III 57.9 25.2 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0028 NM_012249 Huesken TC10 23433 AGUCAUCCAGUAGACUCUCuc GAGAGUCUACUGGAUGACU -2.4 -2.1 -3 2 3 2 -39 52.8 10.1 3 Ib 47.4 55.6 77.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0029 NM_012249 Huesken TC10 23433 AGACUCUCUCCACUCUUCAau UGAAGAGUGGAGAGAGUCU -2.1 -2.1 1.2 3 1 2 -39.8 66 -1.4 6 II 47.4 52.6 70.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0030 NM_012249 Huesken TC10 23433 GGAAGGUGAUGCUUAUAUUuu AAUAUAAGCAUCACCUUCC -0.9 -3.3 1.9 1 -1 2 -34 66.1 -4 3 III 36.8 38 51.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0031 NM_012249 Huesken TC10 23433 UCUACAAAGCUCACAUACAac UGUAUGUGAGCUUUGUAGA -2.1 -2.4 1.2 1 0 2 -35 65.7 -8.7 6 II 36.8 57.8 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0032 NM_012249 Huesken TC10 23433 CAACAAGACAGUACAUCCUag AGGAUGUACUGUCUUGUUG -2.1 -2.1 -1.8 1 0 2 -35.8 58.6 -2.8 4 II 42.1 51.4 81.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0033 NM_012249 Huesken TC10 23433 ACAGUACAUCCUAGAUUUGug CAAAUCUAGGAUGUACUGU -2.1 -2.2 -0.3 0 2 2 -33.9 58.5 -1.9 5 Ib 36.8 49.5 79.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0034 NM_012249 Huesken TC10 23433 UCCUAGAUUUGUGACUGAUau AUCAGUCACAAAUCUAGGA -1.1 -2.4 1.5 0 0 2 -35.2 69.7 1.8 6 II 36.8 50.2 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0035 NM_012249 Huesken TC10 23433 UUUGUGACUGAUAUGAGCAuu UGCUCAUAUCAGUCACAAA -2.1 -0.9 0.9 0 3 2 -35 81.4 1.3 7 II 36.8 71.6 83.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0036 NM_012249 Huesken TC10 23433 UGUGACUGAUAUGAGCAUUua AAUGCUCAUAUCAGUCACA -0.9 -2.1 0.9 1 0 2 -35.2 71.3 4.1 6 II 36.8 56 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0037 NM_012249 Huesken TC10 23433 GCAUUUAAGGCUGUCAUUUuc AAAUGACAGCCUUAAAUGC -0.9 -3.4 1.5 1 -1 3 -33.2 70.1 -1 5 II 36.8 44.3 42.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0038 NM_012249 Huesken TC10 23433 UUUAAGGCUGUCAUUUUCAag UGAAAAUGACAGCCUUAAA -2.1 -0.9 2.4 0 2 3 -32 81.7 -3.7 9 II 31.6 71.2 78.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0039 NM_012249 Huesken TC10 23433 UUAAGGCUGUCAUUUUCAAgu UUGAAAAUGACAGCCUUAA -0.9 -0.9 2.1 1 2 3 -32 76.1 -3.8 6 II 31.6 55.5 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0040 NM_012249 Huesken TC10 23433 AAGUAUAAAAGUUUAGUGUuc ACACUAAACUUUUAUACUU -2.2 -0.9 2.9 1 2 1 -27.6 99.4 4.1 8 II 21.1 65.3 76.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0041 NM_012249 Huesken TC10 23433 UAAAAGUUUAGUGUUCCAUua AUGGAACACUAAACUUUUA -1.1 -1.3 0.8 1 3 2 -29.8 92.4 4.1 9 II 26.3 70.5 82.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0042 NM_012249 Huesken TC10 23433 GUGUUCCAUUACCCAAUCUgu AGAUUGGGUAAUGGAACAC -2.1 -2.2 1 0 -1 3 -35.9 69.2 -1.6 4 III 42.1 43.2 72 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0043 NM_012249 Huesken TC10 23433 UGUUCCAUUACCCAAUCUGug CAGAUUGGGUAAUGGAACA -2.1 -2.1 1 0 3 3 -35.8 80.3 -2.3 7 Ib 42.1 67.6 86.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0044 NM_012249 Huesken TC10 23433 GUUCCAUUACCCAAUCUGUgc ACAGAUUGGGUAAUGGAAC -2.2 -2.2 1.5 2 0 3 -35.9 65.3 -11.3 4 II 42.1 45.1 47.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0045 NM_012249 Huesken TC10 23433 UGUGCAGUAGACAUAGCUAua UAGCUAUGUCUACUGCACA -1.3 -2.1 -0.8 0 1 2 -37.6 63.8 -4.1 5 II 42.1 52 86.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0046 NM_012249 Huesken TC10 23433 UGCAGUAGACAUAGCUAUAag UAUAGCUAUGUCUACUGCA -1.3 -2.1 -0.8 -1 -2 2 -35.7 67.8 -1 5 II 36.8 50.5 77.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0047 NM_012249 Huesken TC10 23433 UAGCUAUAAGCUCAAGUCAug UGACUUGAGCUUAUAGCUA -2.1 -1.3 -2.2 2 0 2 -35.3 73.6 -0.7 6 II 36.8 62.6 84.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0048 NM_012249 Huesken TC10 23433 AUAAGCUCAAGUCAUGUGAau UCACAUGACUUGAGCUUAU -2.4 -1.1 0.8 2 1 2 -35 80.5 1.7 8 II 36.8 59.9 87 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0049 NM_012249 Huesken TC10 23433 CUCAAGUCAUGUGAAUUAAca UUAAUUCACAUGACUUGAG -0.9 -2.1 0.7 0 -4 1 -31.3 69.2 0 5 II 31.6 37.5 54.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0050 NM_012249 Huesken TC10 23433 UAUAAUUUGGGCAACAGCAag UGCUGUUGCCCAAAUUAUA -2.1 -1.3 -0.6 2 2 4 -34.5 79.6 -6 8 II 36.8 72.2 85.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0051 NM_012249 Huesken TC10 23433 AUAAUUUGGGCAACAGCAAgu UUGCUGUUGCCCAAAUUAU -0.9 -1.1 -0.6 3 1 4 -34.1 65 -8.7 7 II 36.8 56 83.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0052 NM_012249 Huesken TC10 23433 GCAACAGCAAGUUUAAAUGua CAUUUAAACUUGCUGUUGC -2.1 -3.4 0 0 1 2 -31.6 74.9 5.4 4 II 36.8 47.8 74.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0053 NM_012249 Huesken TC10 23433 ACAGCAAGUUUAAAUGUAGga CUACAUUUAAACUUGCUGU -2.1 -2.2 1.5 1 2 2 -30.8 61.6 -2.6 5 Ib 31.6 55.4 82.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0054 NM_012249 Huesken TC10 23433 AUUGUUUCUCUAAAAUGCAuu UGCAUUUUAGAGAAACAAU -2.1 -1.1 2.2 2 2 2 -29.8 77.4 -6.3 6 II 26.3 65.2 84.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0055 NM_012249 Huesken TC10 23433 AUGCAUUAGGUUGUUCACAau UGUGAACAACCUAAUGCAU -2.1 -1.1 -0.2 4 1 2 -34.5 69.7 4.3 5 II 36.8 59.7 75.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0056 NM_012249 Huesken TC10 23433 UGCAUUAGGUUGUUCACAAug UUGUGAACAACCUAAUGCA -0.9 -2.1 -0.8 1 0 2 -34.3 76.2 -1.4 6 II 36.8 54.5 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0057 NM_012249 Huesken TC10 23433 UAACACCAUUAUCUGAUGCau GCAUCAGAUAAUGGUGUUA -3.4 -1.3 -4.7 1 5 2 -34.1 85.5 20.2 6 Ib 36.8 71.6 92.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0058 NM_012249 Huesken TC10 23433 AACACCAUUAUCUGAUGCAuc UGCAUCAGAUAAUGGUGUU -2.1 -0.9 -4.9 0 1 2 -34.9 74 -6.1 5 II 36.8 55.2 61.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0059 NM_012249 Huesken TC10 23433 CAUUAUCUGAUGCAUCCAUua AUGGAUGCAUCAGAUAAUG -1.1 -2.1 1.2 0 -1 2 -34.2 70.3 -0.9 5 II 36.8 44.9 82.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0060 NM_012249 Huesken TC10 23433 UAUCUGAUGCAUCCAUUAUcu AUAAUGGAUGCAUCAGAUA -1.1 -1.3 1.1 2 1 2 -33.4 87 3.8 8 II 31.6 61.3 80.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0061 NM_012249 Huesken TC10 23433 CUGAUGCAUCCAUUAUCUGau CAGAUAAUGGAUGCAUCAG -2.1 -2.1 0.7 -1 1 2 -35.2 65.1 -2 3 II 42.1 51.3 80.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0062 NM_012249 Huesken TC10 23433 AUCCAUUAUCUGAUGCAUGgc CAUGCAUCAGAUAAUGGAU -2.1 -1.1 0.3 3 3 2 -34.2 73.3 2.4 5 Ia 36.8 66.5 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0063 NM_012249 Huesken TC10 23433 CAUUAUCUGAUGCAUGGCAua UGCCAUGCAUCAGAUAAUG -2.1 -2.1 0.1 0 -1 3 -36.2 65.8 -0.7 5 II 42.1 45.8 59.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0064 NM_012249 Huesken TC10 23433 UUAUCUGAUGCAUGGCAUAug UAUGCCAUGCAUCAGAUAA -1.3 -0.9 -0.7 -1 0 3 -35.4 70.9 -6.1 7 II 36.8 59.7 75.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0065 NM_012249 Huesken TC10 23433 AUGCAAUAAGGCAGAUCCAca UGGAUCUGCCUUAUUGCAU -2.1 -1.1 -1.1 2 1 3 -37.2 51.8 -6 4 II 42.1 50.4 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0066 NM_012249 Huesken TC10 23433 GCAAUAAGGCAGAUCCACAgc UGUGGAUCUGCCUUAUUGC -2.1 -3.4 -0.2 1 -1 3 -38.3 50.9 -1.7 4 II 47.4 39.8 68.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0067 NM_012249 Huesken TC10 23433 CAAUAAGGCAGAUCCACAGca CUGUGGAUCUGCCUUAUUG -2.1 -2.1 -0.2 0 1 3 -37 61 0.7 6 II 47.4 52.8 79 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0068 NM_004359 Huesken CDC34 997 CGUCCCGUAGUAGUCGUCGua CGACGACUACUACGGGACG -2.4 -2.4 0.6 0 1 4 -41.2 47.7 0.3 2 II 63.2 47 62.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0069 NM_004359 Huesken CDC34 997 CCCGUAGUAGUCGUCGUAGaa CUACGACGACUACUACGGG -2.1 -3.3 0.6 -1 -1 4 -39.8 44.2 -2 2 II 57.9 38.2 69 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0070 NM_004359 Huesken CDC34 997 GUAGUCGUCGUAGAAGAGGuc CCUCUUCUACGACGACUAC -3.3 -2.2 1.4 1 2 2 -38.4 46 0 4 II 52.6 53 82.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0071 NM_004359 Huesken CDC34 997 UAGUCGUCGUAGAAGAGGUcu ACCUCUUCUACGACGACUA -2.2 -1.3 1.4 2 2 2 -38.4 67.7 -4.3 6 II 47.4 62.9 89.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0072 NM_004359 Huesken CDC34 997 GUCGUAGAAGAGGUCUGAGcc CUCAGACCUCUUCUACGAC -2.1 -2.2 0.4 0 2 2 -39.1 50 4.6 3 II 52.6 39.7 37.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0073 NM_004359 Huesken CDC34 997 AGAGGUCUGAGCCCUCGUCgg GACGAGGGCUCAGACCUCU -2.4 -2.1 -5.8 2 3 4 -44.7 48.9 7.5 2 II 63.2 53 51.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0074 NM_004359 Huesken CDC34 997 GUCUGAGCCCUCGUCGGGCgc GCCCGACGAGGGCUCAGAC -3.4 -2.2 -7.8 1 3 5 -47.2 35.3 7.4 1 II 73.7 43.3 33.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0075 NM_004359 Huesken CDC34 997 GUCGGGCGCCGGCGCCUUGgu CAAGGCGCCGGCGCCCGAC -2.1 -2.2 -6.9 0 0 14 -49.4 18.3 2.4 0 II 84.2 30.7 26.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0076 NM_004359 Huesken CDC34 997 GCGCCGGCGCCUUGGUCUUca AAGACCAAGGCGCCGGCGC -0.9 -3.4 -2.6 1 -2 11 -46.7 25.6 -3.3 -1 III 73.7 21.7 25.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0077 NM_004359 Huesken CDC34 997 UGGUCUUCACGCAGUACUCgg GAGUACUGCGUGAAGACCA -2.4 -2.1 0.3 0 2 3 -39.9 68.2 2.5 5 Ib 52.6 62.3 73.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0078 NM_004359 Huesken CDC34 997 GUCUUCACGCAGUACUCGGcc CCGAGUACUGCGUGAAGAC -3.3 -2.2 0.3 1 2 3 -40.2 61.4 2.3 3 II 57.9 49.6 59 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0079 NM_004359 Huesken CDC34 997 UUCACGCAGUACUCGGCCAgc UGGCCGAGUACUGCGUGAA -2.1 -0.9 -0.3 1 1 5 -42.3 58.9 -3.8 4 II 57.9 54.1 65.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0080 NM_004359 Huesken CDC34 997 CGCAGUACUCGGCCAGCGUgg ACGCUGGCCGAGUACUGCG -2.2 -2.4 -1.6 -1 -2 5 -44.8 37.9 -3.6 0 III 68.4 34.3 52.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0081 NM_004359 Huesken CDC34 997 GUCACGCUCCGCGUCCACCuu GGUGGACGCGGAGCGUGAC -3.3 -2.2 -2.9 1 2 5 -46.2 45.4 7.4 0 II 73.7 46.3 53.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0082 NM_004359 Huesken CDC34 997 CCUUGGUCCCCAGGACCUGcu CAGGUCCUGGGGACCAAGG -2.1 -3.3 -7.4 0 0 4 -45.8 28.9 -4.4 1 II 68.4 37.3 43 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0083 NM_004359 Huesken CDC34 997 GUCCCCAGGACCUGCUUCCgg GGAAGCAGGUCCUGGGGAC -3.3 -2.2 -2.2 1 1 4 -46.2 48.2 2.7 2 II 68.4 47.5 58.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0084 NM_004359 Huesken CDC34 997 GCUUCCGGAUGAUGUCUGUgu ACAGACAUCAUCCGGAAGC -2.2 -3.4 1.2 -1 -1 4 -40 52.9 -4 4 III 52.6 27.2 34.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0085 NM_004359 Huesken CDC34 997 GAUGAUGUCUGUGUACUCCcg GGAGUACACAGACAUCAUC -3.3 -2.4 0.7 1 3 2 -37.8 69.5 15.5 5 II 47.4 55.1 76.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0086 NM_004359 Huesken CDC34 997 UGUGUACUCCCGAUCCUUCcc GAAGGAUCGGGAGUACACA -2.4 -2.1 1.2 1 3 4 -40.2 66.1 4.8 6 Ib 52.6 62.6 74.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0087 NM_004359 Huesken CDC34 997 GUGUACUCCCGAUCCUUCCcc GGAAGGAUCGGGAGUACAC -3.3 -2.2 1.2 2 1 4 -41.4 67.7 10.1 4 II 57.9 55.5 56.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0088 NM_004359 Huesken CDC34 997 CCCGAUCCUUCCCCUUGCUcu AGCAAGGGGAAGGAUCGGG -2.1 -3.3 -0.9 -1 -2 4 -44.1 39.7 -5.6 0 III 63.2 30.7 41.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0089 NM_004359 Huesken CDC34 997 UUUCCACUUCCUGUACAUCac GAUGUACAGGAAGUGGAAA -2.4 -0.9 0.4 1 4 2 -36 75.1 10.4 5 Ib 42.1 64.9 82.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0090 NM_004359 Huesken CDC34 997 CCUGUACAUCACGGAGGCGuc CGCCUCCGUGAUGUACAGG -2.4 -3.3 -0.3 -2 1 4 -42.4 31 -2.1 1 II 63.2 35.3 36.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0091 NM_004359 Huesken CDC34 997 CAUCACGGAGGCGUCCACGuu CGUGGACGCCUCCGUGAUG -2.4 -2.1 -2.9 0 2 4 -43.8 41.4 0.7 2 II 68.4 49.6 79.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0092 NM_004359 Huesken CDC34 997 UCACGGAGGCGUCCACGUUug AACGUGGACGCCUCCGUGA -0.9 -2.4 -3.4 2 1 4 -43.7 38.9 1.5 3 II 63.2 48.6 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0093 NM_004359 Huesken CDC34 997 CGGGCGAGAAGGUGUUGGGcu CCCAACACCUUCUCGCCCG -3.3 -2.4 4.6 -2 0 6 -44.1 37.9 -2 1 II 68.4 37.9 45.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0094 NM_004359 Huesken CDC34 997 GUUGGGCUCGUUCAGGAGGga CCUCCUGAACGAGCCCAAC -3.3 -2.2 -0.7 1 2 4 -42.9 45 5.4 1 II 63.2 46.9 68.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0095 NM_004359 Huesken CDC34 997 UCGUUCAGGAGGGAGAUCAca UGAUCUCCCUCCUGAACGA -2.1 -2.4 0.6 1 -1 3 -41.4 59.7 -3.8 8 II 52.6 56.7 70 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0096 NM_004359 Huesken CDC34 997 GGAGGGAGAUCACACUCAGga CUGAGUGUGAUCUCCCUCC -2.1 -3.3 -1.4 0 1 3 -42.1 33.2 0.1 0 II 57.9 37.1 23.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0097 NM_004359 Huesken CDC34 997 GAGGGAGAUCACACUCAGGag CCUGAGUGUGAUCUCCCUC -3.3 -2.4 -1.4 0 1 3 -42.1 40.2 -2.6 0 II 57.9 44.9 58.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0098 NM_004359 Huesken CDC34 997 GGGAGAUCACACUCAGGAGaa CUCCUGAGUGUGAUCUCCC -2.1 -3.3 -1.4 1 0 3 -42.1 48.2 -0.1 0 II 57.9 34.7 42.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0099 NM_004359 Huesken CDC34 997 UCACACUCAGGAGAAUGGUcc ACCAUUCUCCUGAGUGUGA -2.2 -2.4 -3.8 2 2 2 -39.5 52.6 -1.3 5 II 47.4 55.2 81.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0100 NM_004359 Huesken CDC34 997 CACACUCAGGAGAAUGGUCcu GACCAUUCUCCUGAGUGUG -2.4 -2.1 -3.8 0 0 2 -39.5 55.8 5.1 1 II 52.6 47.3 44.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0101 NM_004359 Huesken CDC34 997 CAGGAGAAUGGUCCUGACGuu CGUCAGGACCAUUCUCCUG -2.4 -2.1 -4.8 -1 0 2 -40.9 51.1 6.1 1 II 57.9 53.3 72.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0102 NM_004359 Huesken CDC34 997 AGGAGAAUGGUCCUGACGUuc ACGUCAGGACCAUUCUCCU -2.2 -2.1 -2.4 2 2 2 -41 52.4 -1.6 3 II 52.6 51.6 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0103 NM_004359 Huesken CDC34 997 CUGACGUUCUGCGUGGGGUuc ACCCCACGCAGAACGUCAG -2.2 -2.1 0 1 0 4 -43.1 52.4 -6 2 III 63.2 43 57.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0104 NM_004359 Huesken CDC34 997 UCUGCGUGGGGUUCCACCUcu AGGUGGAACCCCACGCAGA -2.1 -2.4 -5.2 2 2 4 -45.1 58.4 -1 3 II 63.2 60 72.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0105 NM_004359 Huesken CDC34 997 CCACCUCUCUGAGGGCAGCuc GCUGCCCUCAGAGAGGUGG -3.4 -3.3 -3.2 0 0 4 -46.2 33.2 5.4 -1 II 68.4 36.1 39.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0106 NM_004359 Huesken CDC34 997 GGUCGUCCACCGGCGGGUGga CACCCGCCGGUGGACGACC -2.1 -3.3 -4.2 1 1 8 -48.2 23.4 -2.4 -1 II 78.9 27.8 25.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0107 NM_004359 Huesken CDC34 997 GUCGUCCACCGGCGGGUGGag CCACCCGCCGGUGGACGAC -3.3 -2.2 -7.3 0 1 8 -48.2 32.5 2.4 1 II 78.9 33.5 44.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0108 NM_004359 Huesken CDC34 997 CGUAGAUGUUAGGGUGCCAca UGGCACCCUAACAUCUACG -2.1 -2.4 1.2 -1 -2 3 -39.8 42.1 -3.5 3 II 52.6 31.1 25.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0109 NM_004359 Huesken CDC34 997 UGUUAGGGUGCCACAUCUUgg AAGAUGUGGCACCCUAACA -0.9 -2.1 0.9 0 1 3 -39.1 56.3 -8.6 7 II 47.4 55.3 36.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0110 NM_004359 Huesken CDC34 997 GUGGAGAGUAUGGGUAGUCga GACUACCCAUACUCUCCAC -2.4 -2.2 2.7 -1 1 3 -40.1 40.6 10.1 4 II 52.6 48.3 65.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0111 NM_004359 Huesken CDC34 997 GUAUGGGUAGUCGAUGGGGaa CCCCAUCGACUACCCAUAC -3.3 -2.2 4.1 0 3 4 -41.4 42.3 -2.4 3 II 57.9 49.2 44.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0112 NM_004359 Huesken CDC34 997 GAUGGGGAACUUGAGGCGCgc GCGCCUCAAGUUCCCCAUC -3.4 -2.4 1.6 0 3 5 -43.1 36.5 10.4 2 II 63.2 47.2 58 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0113 NM_004359 Huesken CDC34 997 AUGGGGAACUUGAGGCGCGcc CGCGCCUCAAGUUCCCCAU -2.4 -1.1 1.3 1 4 6 -43.1 34.7 -2.6 3 II 63.2 59.3 51.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0114 NM_004359 Huesken CDC34 997 CGCCUUGAAGUAGCCGCCCuc GGGCGGCUACUUCAAGGCG -3.3 -2.4 -1.8 0 0 7 -44.3 34.4 5.4 0 II 68.4 47.1 29.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0115 NM_004359 Huesken CDC34 997 GAAGUAGCCGCCCUCGUAGua CUACGAGGGCGGCUACUUC -2.1 -2.4 -1.9 1 2 7 -42.6 47.6 0 3 II 63.2 45.1 59.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0116 NM_004359 Huesken CDC34 997 AAGUAGCCGCCCUCGUAGUag ACUACGAGGGCGGCUACUU -2.2 -0.9 0 2 1 7 -42.4 52.7 -6 4 II 57.9 47.2 73.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0117 NM_004359 Huesken CDC34 997 CCUCCCAGUUGUAUAGAUCgc GAUCUAUACAACUGGGAGG -2.4 -3.3 -0.1 0 0 3 -37.7 62.4 8.2 2 II 47.4 44.2 41.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0118 NM_004359 Huesken CDC34 997 UCCCAGUUGUAUAGAUCGCcc GCGAUCUAUACAACUGGGA -3.4 -2.4 -0.1 2 3 3 -38.1 60.7 12.8 5 II 47.4 59.4 74 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0119 NM_004359 Huesken CDC34 997 GUUGUAUAGAUCGCCCUCGuc CGAGGGCGAUCUAUACAAC -2.4 -2.2 -0.1 2 2 5 -38.4 58.2 -2.4 6 II 52.6 58.7 72.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0120 NM_004359 Huesken CDC34 997 UGUAUAGAUCGCCCUCGUCca GACGAGGGCGAUCUAUACA -2.4 -2.1 -0.1 0 3 5 -39.9 64.6 7.5 7 Ia 52.6 61.2 64.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0121 NM_004359 Huesken CDC34 997 UCGCCCUCGUCCACCAGUGuc CACUGGUGGACGAGGGCGA -2.1 -2.4 0.3 3 2 5 -45.7 46.1 -7.3 3 II 68.4 56.7 75.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0122 NM_004359 Huesken CDC34 997 CGUCCACCAGUGUCACGCGga CGCGUGACACUGGUGGACG -2.4 -2.4 -0.4 0 1 4 -43.5 37.9 -2 0 II 68.4 38.9 67.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0123 NM_004359 Huesken CDC34 997 CCCUCGACCGGCUCUUCCUgc AGGAAGAGCCGGUCGAGGG -2.1 -3.3 -1.6 0 -2 5 -45.8 48 -8.3 0 III 68.4 37.7 44.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0124 NM_004359 Huesken CDC34 997 CGGCUCUUCCUGCAGCCCCuu GGGGCUGCAGGAAGAGCCG -3.3 -2.4 -5.6 2 0 5 -47.4 41.9 7.8 0 II 73.7 49.5 47.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0125 NM_003340 Huesken UBE2D3 7323 GUCUGUUUUAUAGAUCCGUgc ACGGAUCUAUAAAACAGAC -2.2 -2.2 0.8 1 0 3 -33.3 68.4 -4 4 II 36.8 51.4 68.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0126 NM_003340 Huesken UBE2D3 7323 UUUAUAGAUCCGUGCAAUCuc GAUUGCACGGAUCUAUAAA -2.4 -0.9 -0.7 -1 3 3 -33.4 77.6 5.1 8 Ia 36.8 71.1 92.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0127 NM_003340 Huesken UBE2D3 7323 AGAUCCGUGCAAUCUCUGGca CCAGAGAUUGCACGGAUCU -3.3 -2.1 -1.5 2 3 3 -39.9 67.4 2.3 5 II 52.6 56.3 82 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0128 NM_003340 Huesken UBE2D3 7323 CGUGCAAUCUCUGGCACUAgg UAGUGCCAGAGAUUGCACG -1.3 -2.4 -4.8 -1 -3 3 -39.7 43.5 -5.1 1 III 52.6 29.4 62.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0129 NM_003340 Huesken UBE2D3 7323 UGCAAUCUCUGGCACUAGGgg CCUAGUGCCAGAGAUUGCA -3.3 -2.1 -0.4 1 2 3 -40.5 66.3 5.1 5 Ib 52.6 59.2 86.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0130 NM_003340 Huesken UBE2D3 7323 GGGUCAUCUGGGUUUGGAUca AUCCAAACCCAGAUGACCC -1.1 -3.3 0.9 1 -1 3 -40.5 60.4 -1.6 2 III 52.6 28.8 44.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0131 NM_003340 Huesken UBE2D3 7323 GGUCAUCUGGGUUUGGAUCac GAUCCAAACCCAGAUGACC -2.4 -3.3 0.5 2 1 3 -39.6 64.6 15.5 2 II 52.6 41.2 56.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0132 NM_003340 Huesken UBE2D3 7323 CUGGGUUUGGAUCACAUAGca CUAUGUGAUCCAAACCCAG -2.1 -2.1 1.5 1 -1 3 -37 67.6 5.7 3 II 47.4 54.8 95.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0133 NM_003340 Huesken UBE2D3 7323 GGGUUUGGAUCACAUAGCAgu UGCUAUGUGAUCCAAACCC -2.1 -3.3 1.5 0 -2 3 -38.3 51.7 -3.7 3 III 47.4 33.6 42.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0134 NM_003340 Huesken UBE2D3 7323 UUGGAUCACAUAGCAGUGAac UCACUGCUAUGUGAUCCAA -2.4 -0.9 -3.4 1 0 2 -37.4 59.8 -1.1 6 II 42.1 60.8 95.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0135 NM_003340 Huesken UBE2D3 7323 CAUAGCAGUGAACAAAUGGau CCAUUUGUUCACUGCUAUG -3.3 -2.1 1.1 -1 1 2 -34.4 65 2.7 5 II 42.1 57.5 94.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0136 NM_003340 Huesken UBE2D3 7323 AUAGCAGUGAACAAAUGGAua UCCAUUUGUUCACUGCUAU -2.4 -1.1 1.1 2 2 2 -34.7 61.8 -6.4 6 II 36.8 56.1 98.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0137 NM_003340 Huesken UBE2D3 7323 UAGCAGUGAACAAAUGGAUaa AUCCAUUUGUUCACUGCUA -1.1 -1.3 1.1 2 1 2 -34.7 63.7 -6.2 7 II 36.8 61.1 96.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0138 NM_003340 Huesken UBE2D3 7323 GCAGUGAACAAAUGGAUAAaa UUAUCCAUUUGUUCACUGC -0.9 -3.4 2.3 0 -3 2 -33.5 57.5 -1.5 5 III 36.8 35.5 23.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0139 NM_003340 Huesken UBE2D3 7323 GUGAACAAAUGGAUAAAAGaa CUUUUAUCCAUUUGUUCAC -2.1 -2.2 3 0 1 2 -29.8 71.2 2.4 4 II 31.6 48.7 27 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0140 NM_003340 Huesken UBE2D3 7323 UGGAUAAAAGAACUUUAGAaa UCUAAAGUUCUUUUAUCCA -2.4 -2.1 2.3 0 0 2 -30.2 81.8 3.3 6 II 26.3 57.8 64.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0141 NM_003340 Huesken UBE2D3 7323 GAUAAAAGAACUUUAGAAAuu UUUCUAAAGUUCUUUUAUC -0.9 -2.4 2.3 0 -1 1 -26.6 83 2 6 II 21.1 41.6 30.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0142 NM_003340 Huesken UBE2D3 7323 AAAAGAACUUUAGAAAUUGuu CAAUUUCUAAAGUUCUUUU -2.1 -0.9 2.5 1 3 1 -25.9 73 0 7 Ia 21.1 68.5 80.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0143 NM_003340 Huesken UBE2D3 7323 UUUAGAAAUUGUUAAAGCAgg UGCUUUAACAAUUUCUAAA -2.1 -0.9 1.9 0 2 2 -27.3 88.2 -0.7 7 II 21.1 67.6 92 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0144 NM_003340 Huesken UBE2D3 7323 UUAGAAAUUGUUAAAGCAGgc CUGCUUUAACAAUUUCUAA -2.1 -0.9 1.8 0 4 2 -28.5 76.1 3.1 7 Ia 26.3 75.8 89.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0145 NM_003340 Huesken UBE2D3 7323 AUUGUUAAAGCAGGCGACCac GGUCGCCUGCUUUAACAAU -3.3 -1.1 1.2 0 4 4 -37 59.1 5.1 6 Ia 47.4 67.5 84.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0146 NM_003340 Huesken UBE2D3 7323 UUGUUAAAGCAGGCGACCAcu UGGUCGCCUGCUUUAACAA -2.1 -0.9 1.2 1 1 4 -38 63 -1.5 7 II 47.4 61.5 90.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0147 NM_003340 Huesken UBE2D3 7323 UGUUAAAGCAGGCGACCACug GUGGUCGCCUGCUUUAACA -2.2 -2.1 -0.9 0 3 4 -39.3 58.6 12.5 8 Ia 52.6 57.2 100.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0148 NM_003340 Huesken UBE2D3 7323 GGCGACCACUGUGAUCUUAga UAAGAUCACAGUGGUCGCC -1.3 -3.3 -3.4 1 -4 4 -40 42.6 2 1 III 52.6 21.3 55.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0149 NM_003340 Huesken UBE2D3 7323 CGACCACUGUGAUCUUAGAau UCUAAGAUCACAGUGGUCG -2.4 -2.4 -3.4 1 -3 2 -37.8 51.6 -5.8 0 III 47.4 27.4 43.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0150 NM_003340 Huesken UBE2D3 7323 UGAUCUUAGAAUAUCGAGAca UCUCGAUAUUCUAAGAUCA -2.4 -2.1 -0.5 2 1 2 -32.9 90.6 1.3 7 II 31.6 66.1 98.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0151 NM_003340 Huesken UBE2D3 7323 GAAUAUCGAGACAAAUGCUgc AGCAUUUGUCUCGAUAUUC -2.1 -2.4 1.4 0 1 2 -33.3 62.7 -3.9 4 II 36.8 46.6 79.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0152 NM_003340 Huesken UBE2D3 7323 AAUAUCGAGACAAAUGCUGcc CAGCAUUUGUCUCGAUAUU -2.1 -0.9 1.4 2 4 2 -33 71.4 -4.9 8 Ia 36.8 67.7 95.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0153 NM_003340 Huesken UBE2D3 7323 AUCGAGACAAAUGCUGCCAuu UGGCAGCAUUUGUCUCGAU -2.1 -1.1 -1.7 1 1 3 -38.5 59.8 4.3 5 II 47.4 55.7 99.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0154 NM_003340 Huesken UBE2D3 7323 ACAAAUGCUGCCAUUACUGuu CAGUAAUGGCAGCAUUUGU -2.1 -2.2 -0.4 1 4 3 -35.4 65.3 -2.3 6 Ia 42.1 63.7 97.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0155 NM_003340 Huesken UBE2D3 7323 UGCUGCCAUUACUGUUAAUau AUUAACAGUAAUGGCAGCA -1.1 -2.1 -0.9 -1 -1 3 -34.6 70.9 -4 4 II 36.8 41.1 57.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0156 NM_003340 Huesken UBE2D3 7323 CUGUUAAUAUUUGGAUGAUaa AUCAUCCAAAUAUUAACAG -1.1 -2.1 3.8 -2 -2 2 -29.3 69.7 -3 4 II 26.3 37.9 32 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0157 NM_003340 Huesken UBE2D3 7323 UAAUAUUUGGAUGAUAAAUuc AUUUAUCAUCCAAAUAUUA -1.1 -1.3 2.5 2 1 2 -26.2 99.4 4.1 8 II 15.8 70.4 76.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0158 NM_003340 Huesken UBE2D3 7323 UUUGGAUGAUAAAUUCUUGuu CAAGAAUUUAUCAUCCAAA -2.1 -0.9 1 1 4 2 -28.9 86.7 2 7 Ia 26.3 73.2 93.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0159 NM_003340 Huesken UBE2D3 7323 GAUAAAUUCUUGUUGUAAAug UUUACAACAAGAAUUUAUC -0.9 -2.4 2.7 2 -1 1 -26.6 87.6 1.3 5 II 21.1 41.6 48.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0160 NM_003340 Huesken UBE2D3 7323 AUAAAUUCUUGUUGUAAAUgc AUUUACAACAAGAAUUUAU -1.1 -1.1 2.4 1 1 1 -25.3 96.6 1.8 7 II 15.8 59.7 74.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0161 NM_003340 Huesken UBE2D3 7323 UAAAUUCUUGUUGUAAAUGca CAUUUACAACAAGAAUUUA -2.1 -1.3 2.2 0 4 1 -26.3 97 5.4 7 Ia 21.1 78.7 70 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0162 NM_003340 Huesken UBE2D3 7323 AAUUCUUGUUGUAAAUGCAac UGCAUUUACAACAAGAAUU -2.1 -0.9 1.9 2 2 2 -29.6 88.6 -3.3 6 II 26.3 58.9 83.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0163 NM_003340 Huesken UBE2D3 7323 AUUCUUGUUGUAAAUGCAAcc UUGCAUUUACAACAAGAAU -0.9 -1.1 1.3 2 1 2 -29.6 73.3 -6.3 6 II 26.3 57 68.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0164 NM_003340 Huesken UBE2D3 7323 CUUGUUGUAAAUGCAACCUua AGGUUGCAUUUACAACAAG -2.1 -2.1 -2.6 -1 0 2 -32.8 76.3 -0.7 4 II 36.8 57.3 86.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0165 NM_003340 Huesken UBE2D3 7323 UUGUUGUAAAUGCAACCUUag AAGGUUGCAUUUACAACAA -0.9 -0.9 -2.6 1 1 2 -31.6 79.9 -1.6 7 II 31.6 70.7 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0166 NM_003340 Huesken UBE2D3 7323 GUUGUAAAUGCAACCUUAGgu CUAAGGUUGCAUUUACAAC -2.1 -2.2 -0.9 0 1 2 -32 65.2 -4.9 5 II 36.8 51.4 80.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0167 NM_003340 Huesken UBE2D3 7323 CAACCUUAGGUGGUUUGAAgg UUCAAACCACCUAAGGUUG -0.9 -2.1 -3 2 -1 2 -35.2 59.3 -3.4 2 II 42.1 39.2 64.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0168 NM_003340 Huesken UBE2D3 7323 ACCUUAGGUGGUUUGAAGGgg CCUUCAAACCACCUAAGGU -3.3 -2.2 -1.4 1 3 2 -37.6 71.5 5.4 4 Ib 47.4 54.8 94.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0169 NM_003340 Huesken UBE2D3 7323 GGUGGUUUGAAGGGGUAGUcu ACUACCCCUUCAAACCACC -2.2 -3.3 1 -1 4 -40.1 50.1 -1.7 3 III 52.6 35.6 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0170 NM_003340 Huesken UBE2D3 7323 GUGGUUUGAAGGGGUAGUCug GACUACCCCUUCAAACCAC -2.4 -2.2 1.3 0 1 4 -39.2 55.3 7.4 4 II 52.6 48.6 87.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0171 NM_003340 Huesken UBE2D3 7323 UUGAAGGGGUAGUCUGUAGga CUACAGACUACCCCUUCAA -2.1 -0.9 1.1 1 2 4 -38.3 68.4 5 8 Ib 47.4 62.9 94.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0172 NM_003340 Huesken UBE2D3 7323 UGAAGGGGUAGUCUGUAGGaa CCUACAGACUACCCCUUCA -3.3 -2.1 1.1 0 4 4 -40.7 67.4 7.8 7 II 52.6 67 99.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0173 NM_003340 Huesken UBE2D3 7323 UAGUCUGUAGGAAAAUGAAuu UUCAUUUUCCUACAGACUA -0.9 -1.3 2 0 0 2 -32.7 75.2 -6.3 6 II 31.6 55.7 85 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0174 NM_003340 Huesken UBE2D3 7323 GUCUGUAGGAAAAUGAAUUgu AAUUCAUUUUCCUACAGAC -0.9 -2.2 2 1 -1 2 -31.3 74.3 -1.9 4 II 31.6 49.8 62.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0175 NM_003340 Huesken UBE2D3 7323 CUGUAGGAAAAUGAAUUGUca ACAAUUCAUUUUCCUACAG -2.2 -2.1 3.5 -1 -2 2 -31 70.2 2.1 6 III 31.6 49.9 76.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0176 NM_003340 Huesken UBE2D3 7323 UGUAGGAAAAUGAAUUGUCaa GACAAUUCAUUUUCCUACA -2.4 -2.1 1.3 0 3 2 -31.3 75.6 4.8 7 Ib 31.6 72.2 92.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0177 NM_003340 Huesken UBE2D3 7323 GUAGGAAAAUGAAUUGUCAaa UGACAAUUCAUUUUCCUAC -2.1 -2.2 0.8 0 0 2 -31.3 62.6 -4 4 II 31.6 44.9 55.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0178 NM_003340 Huesken UBE2D3 7323 AAAAGAAUACACCGCCUUGau CAAGGCGGUGUAUUCUUUU -2.1 -0.9 1 0 3 5 -34.5 65.6 2.4 7 Ia 42.1 61.3 104.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0179 NM_003340 Huesken UBE2D3 7323 AGAAUACACCGCCUUGAUAug UAUCAAGGCGGUGUAUUCU -1.3 -2.1 0.1 2 0 5 -36.6 63.6 -1.4 5 II 42.1 42.2 99.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0180 NM_003340 Huesken UBE2D3 7323 CUUGAUAUGGGCUGUCAUUag AAUGACAGCCCAUAUCAAG -0.9 -2.1 0.2 -1 -2 4 -36 63.2 -5.6 4 II 42.1 45.8 80 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0181 NM_003340 Huesken UBE2D3 7323 UUGAUAUGGGCUGUCAUUAgg UAAUGACAGCCCAUAUCAA -1.3 -0.9 0.2 2 0 4 -35.2 78.2 -0.8 8 II 36.8 63.3 97.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0182 NM_003340 Huesken UBE2D3 7323 GGGCUGUCAUUAGGUCCCAua UGGGACCUAAUGACAGCCC -2.1 -3.3 -1.2 1 -2 4 -42.9 31.6 -3.8 0 III 57.9 29.3 48.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0183 NM_003340 Huesken UBE2D3 7323 GCUGUCAUUAGGUCCCAUAau UAUGGGACCUAAUGACAGC -1.3 -3.4 1.5 0 -3 3 -38.7 61.6 -3.8 4 III 47.4 36.9 44.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0184 NM_003340 Huesken UBE2D3 7323 UGUCAUUAGGUCCCAUAAUug AUUAUGGGACCUAAUGACA -1.1 -2.1 0.5 3 0 3 -35.2 70.2 -1.2 6 II 36.8 56 64.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0185 NM_003340 Huesken UBE2D3 7323 GGUCCCAUAAUUGUGGCUUgc AAGCCACAAUUAUGGGACC -0.9 -3.3 -1.6 1 0 3 -38 62.9 1.4 2 III 47.4 38.6 52 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0186 NM_003340 Huesken UBE2D3 7323 GUCCCAUAAUUGUGGCUUGcc CAAGCCACAAUUAUGGGAC -2.1 -2.2 -1.6 1 0 3 -36.8 57.7 0 2 II 47.4 41.1 35.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0187 NM_003340 Huesken UBE2D3 7323 UCCCAUAAUUGUGGCUUGCca GCAAGCCACAAUUAUGGGA -3.4 -2.4 -1.6 0 2 3 -38 63.1 13.1 5 Ib 47.4 59.2 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0188 NM_003340 Huesken UBE2D3 7323 CCCAUAAUUGUGGCUUGCCaa GGCAAGCCACAAUUAUGGG -3.3 -3.3 -1.8 -1 0 3 -38.9 53.8 5.4 2 II 52.6 48.6 60.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0189 NM_003340 Huesken UBE2D3 7323 UAAUUGUGGCUUGCCAAUGaa CAUUGGCAAGCCACAAUUA -2.1 -1.3 -2.4 2 3 3 -35.3 75.5 3 7 Ia 42.1 74.6 100.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0190 NM_003340 Huesken UBE2D3 7323 UUGUGGCUUGCCAAUGAAAca UUUCAUUGGCAAGCCACAA -0.9 -0.9 -2.4 0 -1 3 -36.2 60.8 -11 4 II 42.1 52.6 85.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0191 NM_003340 Huesken UBE2D3 7323 UGUGGCUUGCCAAUGAAACau GUUUCAUUGGCAAGCCACA -2.2 -2.1 -2.4 2 3 3 -37.5 67.8 4.8 4 II 47.4 63.5 94.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0192 NM_003340 Huesken UBE2D3 7323 UGGCUUGCCAAUGAAACAUau AUGUUUCAUUGGCAAGCCA -1.1 -2.1 -1.9 2 0 3 -36.4 67.9 1.4 5 II 42.1 58 90.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0193 NM_003340 Huesken UBE2D3 7323 GGCUUGCCAAUGAAACAUAuc UAUGUUUCAUUGGCAAGCC -1.3 -3.3 -0.9 0 -4 3 -35.6 50.8 -6.3 3 III 42.1 31.1 44.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0194 NM_003340 Huesken UBE2D3 7323 GCCAAUGAAACAUAUCAUCcc GAUGAUAUGUUUCAUUGGC -2.4 -3.4 -2.8 0 -1 3 -32.9 65.4 7.8 3 II 36.8 48.3 66.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0195 NM_003340 Huesken UBE2D3 7323 CAAUGAAACAUAUCAUCCCca GGGAUGAUAUGUUUCAUUG -3.3 -2.1 -3.2 0 2 3 -32.8 70.9 5.4 4 II 36.8 65 95 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0196 NM_003340 Huesken UBE2D3 7323 AUAUCAUCCCCAACUGGACcu GUCCAGUUGGGGAUGAUAU -2.2 -1.1 -3.3 3 4 4 -38.7 67 2.5 5 Ia 47.4 60.7 88.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0197 NM_003340 Huesken UBE2D3 7323 UAUCAUCCCCAACUGGACCug GGUCCAGUUGGGGAUGAUA -3.3 -1.3 -3.7 2 5 4 -40.9 72.5 17.1 5 Ia 52.6 71.8 93.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0198 NM_003340 Huesken UBE2D3 7323 CCCCAACUGGACCUGCAGAac UCUGCAGGUCCAGUUGGGG -2.4 -3.3 -1.5 1 -3 4 -44.7 35.1 1.6 -1 III 63.2 24.7 32.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0199 NM_003340 Huesken UBE2D3 7323 CCCAACUGGACCUGCAGAAca UUCUGCAGGUCCAGUUGGG -0.9 -3.3 -0.9 0 -4 3 -42.3 41.8 -7.8 3 III 57.9 27.3 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0200 NM_003340 Huesken UBE2D3 7323 GACCUGCAGAACAUUGUGCug GCACAAUGUUCUGCAGGUC -3.4 -2.4 -1.8 2 2 2 -39.1 59.8 7.1 3 II 52.6 49 100.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0201 NM_003340 Huesken UBE2D3 7323 ACCUGCAGAACAUUGUGCUgg AGCACAAUGUUCUGCAGGU -2.1 -2.2 -2 1 2 2 -38.8 65.1 -4 4 II 47.4 50.6 101.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0202 NM_003340 Huesken UBE2D3 7323 CCUGCAGAACAUUGUGCUGga CAGCACAAUGUUCUGCAGG -2.1 -3.3 -2 -2 0 2 -38.7 51.2 3.3 1 II 52.6 36.8 87.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0203 NM_003337 Huesken UBE2B 7320 CUUUGUUCAACAAUGGCCGaa CGGCCAUUGUUGAACAAAG -2.4 -2.1 -0.7 0 3 5 -35.3 73.2 -4.6 5 II 47.4 64.5 76.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0204 NM_003337 Huesken UBE2B 7320 GUUCAACAAUGGCCGAAACuc GUUUCGGCCAUUGUUGAAC -2.2 -2.2 -3.1 1 1 5 -35.7 55.5 12.5 2 II 47.4 37.9 61.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0205 NM_003337 Huesken UBE2B 7320 CAAUGGCCGAAACUCUUUUcu AAAAGAGUUUCGGCCAUUG -0.9 -2.1 1.5 0 -1 5 -34.3 66.2 1.1 5 III 42.1 46.5 49.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0206 NM_003337 Huesken UBE2B 7320 AUGGCCGAAACUCUUUUCUca AGAAAAGAGUUUCGGCCAU -2.1 -1.1 -0.8 1 2 5 -35.8 78.2 1.4 6 II 42.1 59.6 77.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0207 NM_003337 Huesken UBE2B 7320 UGGCCGAAACUCUUUUCUCau GAGAAAAGAGUUUCGGCCA -2.4 -2.1 -0.9 1 3 5 -37.1 69.2 7.4 4 II 47.4 64.5 82.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0208 NM_003337 Huesken UBE2B 7320 CGAAACUCUUUUCUCAUAUuc AUAUGAGAAAAGAGUUUCG -1.1 -2.4 -0.9 0 -2 2 -30.6 79.4 4.5 5 II 31.6 45.4 46.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0209 NM_003337 Huesken UBE2B 7320 AAACUCUUUUCUCAUAUUCuc GAAUAUGAGAAAAGAGUUU -2.4 -0.9 3 3 3 1 -29.1 94 10.5 7 Ia 26.3 70.5 78.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0210 NM_003337 Huesken UBE2B 7320 ACUCUUUUCUCAUAUUCUCgu GAGAAUAUGAGAAAAGAGU -2.4 -2.2 4.5 4 3 1 -31.8 85.3 5.1 5 Ia 31.6 63.6 83.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0211 NM_003337 Huesken UBE2B 7320 CUCUUUUCUCAUAUUCUCGuu CGAGAAUAUGAGAAAAGAG -2.4 -2.1 3.1 0 1 2 -32 93.5 3.1 5 II 36.8 64.4 73.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0212 NM_003337 Huesken UBE2B 7320 UCUUUUCUCAUAUUCUCGUuu ACGAGAAUAUGAGAAAAGA -2.2 -2.4 2.6 1 3 2 -32.1 93.7 -1.6 7 II 31.6 67.2 84.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0213 NM_003337 Huesken UBE2B 7320 AUUCUCGUUUGUUUUCCUGau CAGGAAAACAAACGAGAAU -2.1 -1.1 2 5 2 -32.2 88.7 5.4 6 Ib 36.8 64.2 84 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0214 NM_003337 Huesken UBE2B 7320 UUUGUUUUCCUGAUAAAGCug GCUUUAUCAGGAAAACAAA -3.4 -0.9 1.4 2 5 2 -30.8 94.1 7.1 7 Ia 31.6 84.8 80.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0215 NM_003337 Huesken UBE2B 7320 UUUCCUGAUAAAGCUGUGCug GCACAGCUUUAUCAGGAAA -3.4 -0.9 1.1 1 4 2 -35.7 79.5 9.7 8 Ib 42.1 75.9 83.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0216 NM_003337 Huesken UBE2B 7320 UCCUGAUAAAGCUGUGCUGcc CAGCACAGCUUUAUCAGGA -2.1 -2.4 0.3 0 2 2 -38.1 66.5 -2.4 6 Ib 47.4 57.3 77.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0217 NM_003337 Huesken UBE2B 7320 GAUAAAGCUGUGCUGCCUGgc CAGGCAGCACAGCUUUAUC -2.1 -2.4 -2.1 0 3 3 -39.1 54.8 7.4 4 II 52.6 49.5 75.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0218 NM_003337 Huesken UBE2B 7320 AAAGCUGUGCUGCCUGGCUau AGCCAGGCAGCACAGCUUU -2.1 -0.9 -2.1 2 3 3 -43.1 53.3 -1.6 3 II 57.9 55.9 71.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0219 NM_003337 Huesken UBE2B 7320 AGCUGUGCUGCCUGGCUAUug AUAGCCAGGCAGCACAGCU -1.1 -2.1 -1.4 0 -1 3 -43.7 49.5 -8.7 3 II 57.9 38.3 71.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0220 NM_003337 Huesken UBE2B 7320 GCUGUGCUGCCUGGCUAUUgg AAUAGCCAGGCAGCACAGC -0.9 -3.4 -0.9 0 -2 3 -42.5 37.1 -3.3 1 III 57.9 24.4 51 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0221 NM_003337 Huesken UBE2B 7320 UGCUGCCUGGCUAUUGGCUgg AGCCAAUAGCCAGGCAGCA -2.1 -2.1 -4.5 1 2 3 -43.6 59.9 -3.6 2 II 57.9 50.8 75.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0222 NM_003337 Huesken UBE2B 7320 CCUGGCUAUUGGCUGGACUgu AGUCCAGCCAAUAGCCAGG -2.1 -3.3 0.2 0 -1 3 -42.6 50.8 -1.2 1 III 57.9 38.1 68.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0223 NM_003337 Huesken UBE2B 7320 GGACUGUUAGGAUUCGGUUca AACCGAAUCCUAACAGUCC -0.9 -3.3 2.7 2 0 3 -37.5 59.8 -1.6 3 III 47.4 39.9 49.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0224 NM_003337 Huesken UBE2B 7320 GACUGUUAGGAUUCGGUUCau GAACCGAAUCCUAACAGUC -2.4 -2.4 1.9 2 0 3 -36.6 76 12.7 4 II 47.4 51.3 72.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0225 NM_003337 Huesken UBE2B 7320 UUAGGAUUCGGUUCAUCCAgc UGGAUGAACCGAAUCCUAA -2.1 -0.9 -3.5 2 2 3 -36.6 75.1 -0.7 5 II 42.1 66.4 74.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0226 NM_003337 Huesken UBE2B 7320 AGGAUUCGGUUCAUCCAGCag GCUGGAUGAACCGAAUCCU -3.4 -2.1 -3.5 2 3 3 -39.9 58.5 4.8 3 Ib 52.6 58.2 81.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0227 NM_003337 Huesken UBE2B 7320 GGUUCAUCCAGCAGAGACUga AGUCUCUGCUGGAUGAACC -2.1 -3.3 -0.8 1 -1 2 -40.7 55.2 -8.9 4 II 52.6 38.1 53.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0228 NM_003337 Huesken UBE2B 7320 UUCAUCCAGCAGAGACUGAau UCAGUCUCUGCUGGAUGAA -2.4 -0.9 -2.9 0 0 2 -39.7 58.8 -4 6 II 47.4 50.9 62.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0229 NM_003337 Huesken UBE2B 7320 AUCCAGCAGAGACUGAAUUga AAUUCAGUCUCUGCUGGAU -0.9 -1.1 -4.8 3 1 2 -37.2 61 3.5 4 II 42.1 51.2 60.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0230 NM_003337 Huesken UBE2B 7320 CUGAAUUGAUGUUAAGAUAga UAUCUUAACAUCAAUUCAG -1.3 -2.1 4 0 -4 1 -29.4 79.2 0 4 II 26.3 45.7 50.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0231 NM_003337 Huesken UBE2B 7320 UUAAGAUAGAAGAUACAUCau GAUGUAUCUUCUAUCUUAA -2.4 -0.9 -0.1 2 4 1 -30.1 87 9.4 8 Ia 26.3 81.1 84.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0232 NM_003337 Huesken UBE2B 7320 AUAGAAGAUACAUCAUAUGuu CAUAUGAUGUAUCUUCUAU -2.1 -1.1 1.2 1 3 1 -30.2 73.4 0.4 7 Ia 26.3 67.4 83.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0233 NM_003337 Huesken UBE2B 7320 AUACAUCAUAUGUUGGACUcc AGUCCAACAUAUGAUGUAU -2.1 -1.1 0.3 2 3 2 -33.1 79.2 1.1 6 II 31.6 65.8 83.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0234 NM_003337 Huesken UBE2B 7320 AUGUUGGACUCCAUCGAUUcu AAUCGAUGGAGUCCAACAU -0.9 -1.1 -0.3 2 1 2 -36.5 66.1 -8.9 6 II 42.1 56.6 74.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0235 NM_003337 Huesken UBE2B 7320 UGUUGGACUCCAUCGAUUCug GAAUCGAUGGAGUCCAACA -2.4 -2.1 -0.3 0 2 2 -37.8 72 5.1 7 Ib 47.4 67.1 84.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0236 NM_003337 Huesken UBE2B 7320 GUUGGACUCCAUCGAUUCUga AGAAUCGAUGGAGUCCAAC -2.1 -2.2 -0.3 0 0 2 -37.8 57.5 3.8 3 III 47.4 37 64.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0237 NM_003337 Huesken UBE2B 7320 UUGGACUCCAUCGAUUCUGaa CAGAAUCGAUGGAGUCCAA -2.1 -0.9 -0.3 2 3 2 -37.7 67.8 0.4 7 Ib 47.4 74.5 86.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0238 NM_003337 Huesken UBE2B 7320 GACUCCAUCGAUUCUGAAGga CUUCAGAAUCGAUGGAGUC -2.1 -2.4 -2.8 1 0 2 -36.8 78.3 5.3 2 II 47.4 44.7 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0239 NM_003337 Huesken UBE2B 7320 CUCCAUCGAUUCUGAAGGAua UCCUUCAGAAUCGAUGGAG -2.4 -2.1 -2.5 -1 -2 2 -37.9 45.1 -5.4 1 III 47.4 31.7 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0240 NM_003337 Huesken UBE2B 7320 UCCAUCGAUUCUGAAGGAUau AUCCUUCAGAAUCGAUGGA -1.1 -2.4 -0.8 0 0 2 -36.9 60.1 -3.3 6 II 42.1 46.7 77.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0241 NM_003337 Huesken UBE2B 7320 CGAUUCUGAAGGAUAUCUAaa UAGAUAUCCUUCAGAAUCG -1.3 -2.4 0 0 -2 2 -33.8 71 -6 5 II 36.8 41.6 47.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0242 NM_003337 Huesken UBE2B 7320 CUGAAGGAUAUCUAAACAUau AUGUUUAGAUAUCCUUCAG -1.1 -2.1 0 -1 -2 2 -31.8 64.2 -5.6 5 III 31.6 51.3 46.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0243 NM_003337 Huesken UBE2B 7320 UGAAGGAUAUCUAAACAUAug UAUGUUUAGAUAUCCUUCA -1.3 -2.1 0 0 -1 2 -31 71.2 -5.7 6 II 26.3 58.3 63.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0244 NM_003337 Huesken UBE2B 7320 UCUAAACAUAUGCUACCAUca AUGGUAGCAUAUGUUUAGA -1.1 -2.4 0.8 0 2 2 -33 71.8 3.5 7 II 31.6 54.8 69.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0245 NM_003337 Huesken UBE2B 7320 UAUGCUACCAUCAGCAUACac GUAUGCUGAUGGUAGCAUA -2.2 -1.3 -5.4 0 3 2 -36.7 77.8 2.5 7 Ia 42.1 75.7 75.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0246 NM_003337 Huesken UBE2B 7320 CCAUCAGCAUACACAUUUGga CAAAUGUGUAUGCUGAUGG -2.1 -3.3 1.2 -1 -1 2 -34.6 61.7 -4.6 4 II 42.1 43.3 62.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0247 NM_003337 Huesken UBE2B 7320 UCAGCAUACACAUUUGGAUga AUCCAAAUGUGUAUGCUGA -1.1 -2.4 1.2 2 2 2 -34.9 74.6 -4 6 II 36.8 57.6 73 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0248 NM_003337 Huesken UBE2B 7320 GCAUACACAUUUGGAUGAAac UUCAUCCAAAUGUGUAUGC -0.9 -3.4 1.2 -1 -2 2 -33.7 50.5 2 4 II 36.8 23.5 46 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0249 NM_003337 Huesken UBE2B 7320 CACAUUUGGAUGAAACAUUuu AAUGUUUCAUCCAAAUGUG -0.9 -2.1 0.7 1 -3 2 -30.8 71.3 -8.6 5 II 31.6 53.7 63.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0250 NM_003337 Huesken UBE2B 7320 UUUGGAUGAAACAUUUUGGau CCAAAAUGUUUCAUCCAAA -3.3 -0.9 2.2 1 5 2 -30.5 90.2 -0.3 8 Ia 31.6 78 84.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0251 NM_003337 Huesken UBE2B 7320 GGAUGAAACAUUUUGGAUAaa UAUCCAAAAUGUUUCAUCC -1.3 -3.3 2.6 1 -2 2 -31.4 72.3 1.6 4 II 31.6 40.7 48.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0252 NM_003337 Huesken UBE2B 7320 AAAACCUAACAGUUGGUGGuu CCACCAACUGUUAGGUUUU -3.3 -0.9 -1.3 2 5 2 -35 85.9 4.6 6 Ia 42.1 67.4 69.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0253 NM_003337 Huesken UBE2B 7320 AGUUGGUGGUUUAUUUGGAua UCCAAAUAAACCACCAACU -2.4 -2.1 3 2 2 -34.2 69.7 -1 5 II 36.8 47.4 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0254 NM_003337 Huesken UBE2B 7320 GUUUAUUUGGAUAUUCUUCag GAAGAAUAUCCAAAUAAAC -2.4 -2.2 1.9 2 2 2 -28.2 98.8 15.2 6 II 26.3 62.6 77.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0255 NM_003337 Huesken UBE2B 7320 UUAUUUGGAUAUUCUUCAGaa CUGAAGAAUAUCCAAAUAA -2.1 -0.9 1.9 0 4 2 -29.3 100.7 5.3 8 Ia 26.3 71.9 80.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0256 NM_003337 Huesken UBE2B 7320 UUUGGAUAUUCUUCAGAAAau UUUCUGAAGAAUAUCCAAA -0.9 -0.9 0.3 1 0 2 -30.2 81.1 -3.1 6 II 26.3 56.3 82.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0257 NM_003337 Huesken UBE2B 7320 UUGGAUAUUCUUCAGAAAAuu UUUUCUGAAGAAUAUCCAA -0.9 -0.9 0.3 0 -1 2 -30.2 81.7 4.4 6 II 26.3 64.1 85.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0258 NM_003337 Huesken UBE2B 7320 UGGAUAUUCUUCAGAAAAUuc AUUUUCUGAAGAAUAUCCA -1.1 -2.1 0.3 1 -1 2 -30.4 75.7 -8.9 6 II 26.3 56.2 63.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0259 NM_003337 Huesken UBE2B 7320 UCAGAAAAUUCUAUUACUAgu UAGUAAUAGAAUUUUCUGA -1.3 -2.4 -0.8 0 1 1 -28.4 76.1 -0.6 6 II 21.1 58.8 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0260 NM_003337 Huesken UBE2B 7320 AAAAUUCUAUUACUAGUUUaa AAACUAGUAAUAGAAUUUU -0.9 -0.9 -2 1 2 1 -25.5 93.2 0.8 6 II 15.8 61.1 47.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0261 NM_003337 Huesken UBE2B 7320 AAUUCUAUUACUAGUUUAAaa UUAAACUAGUAAUAGAAUU -0.9 -0.9 -2 0 0 1 -25.9 99.5 -5.7 7 II 15.8 55.5 46.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0262 NM_003337 Huesken UBE2B 7320 AUUACUAGUUUAAAAGUACca GUACUUUUAAACUAGUAAU -2.2 -1.1 -1.3 1 3 1 -26.8 86.3 4.8 6 Ia 21.1 69.8 86.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0263 NM_003337 Huesken UBE2B 7320 AUCUUCAAAAGGUGUCCCUuc AGGGACACCUUUUGAAGAU -2.1 -1.1 -1.8 0 2 3 -36.7 74.8 -4 6 II 42.1 57.8 78.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0264 NM_003337 Huesken UBE2B 7320 CUUCAAAAGGUGUCCCUUCug GAAGGGACACCUUUUGAAG -2.4 -2.1 -4 1 0 3 -36.5 58.8 8.1 4 II 47.4 55.6 79.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0265 NM_003337 Huesken UBE2B 7320 UUCUGGUCCAAAUAUAACUgc AGUUAUAUUUGGACCAGAA -2.1 -0.9 0.8 2 1 2 -32.6 89.6 -1.7 7 II 31.6 75.2 79 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0266 NM_003337 Huesken UBE2B 7320 UGGUCCAAAUAUAACUGCAuu UGCAGUUAUAUUUGGACCA -2.1 -2.1 0.1 0 0 2 -34.8 76 -1 5 II 36.8 56.8 81.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0267 NM_003337 Huesken UBE2B 7320 GGUCCAAAUAUAACUGCAUuc AUGCAGUUAUAUUUGGACC -1.1 -3.3 0.1 1 -1 2 -33.8 56.9 -6.6 3 III 36.8 37.1 53.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0268 NM_003337 Huesken UBE2B 7320 AAAUAUAACUGCAUUCCACug GUGGAAUGCAGUUAUAUUU -2.2 -0.9 0.7 2 5 2 -31.4 83.4 7.5 7 Ia 31.6 67.9 84.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0269 NM_003337 Huesken UBE2B 7320 AUAUAACUGCAUUCCACUGca CAGUGGAAUGCAGUUAUAU -2.1 -1.1 0.5 2 4 2 -33.8 79.5 8 6 Ia 36.8 63.5 83.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0270 NM_003337 Huesken UBE2B 7320 CAUUCCACUGCAUGAUGUUgu AACAUCAUGCAGUGGAAUG -0.9 -2.1 -0.1 -2 -1 2 -35.7 63.8 -8.3 4 II 42.1 40.7 55 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0271 NM_003337 Huesken UBE2B 7320 UCCACUGCAUGAUGUUGUUuu AACAACAUCAUGCAGUGGA -0.9 -2.4 -0.1 -1 0 2 -36.8 67.9 -4 5 II 42.1 47.1 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0272 NM_003337 Huesken UBE2B 7320 GCAUGAUGUUGUUUUCAGAug UCUGAAAACAACAUCAUGC -2.4 -3.4 0.6 1 -1 2 -33.4 69.2 1.6 3 II 36.8 34.4 48.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0273 NM_003337 Huesken UBE2B 7320 GAUGUUGUUUUCAGAUGGUgc ACCAUCUGAAAACAACAUC -2.2 -2.4 2 -1 1 2 -33.4 60.5 -8.9 4 II 36.8 43 50.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0274 NM_003337 Huesken UBE2B 7320 UGUUGUUUUCAGAUGGUGCgc GCACCAUCUGAAAACAACA -3.4 -2.1 2 1 4 2 -35.4 88.5 9.4 7 Ia 42.1 72.5 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0275 NM_003337 Huesken UBE2B 7320 UUGUUUUCAGAUGGUGCGCca GCGCACCAUCUGAAAACAA -3.4 -0.9 2 0 4 4 -36.9 79 12.7 7 Ia 47.4 72.2 72.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0276 NM_003337 Huesken UBE2B 7320 UUCAGAUGGUGCGCCACUGac CAGUGGCGCACCAUCUGAA -2.1 -0.9 -2.2 2 3 5 -41.7 55.1 -2.4 4 Ia 57.9 63.7 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0277 NM_003337 Huesken UBE2B 7320 GCCACUGACACCCACAGGUgg ACCUGUGGGUGUCAGUGGC -2.2 -3.4 -1.9 1 -1 3 -44.7 43.7 -6.3 1 III 63.2 37.3 76.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0278 NM_003337 Huesken UBE2B 7320 CACAGGUGGGUCCUCUUGUaa ACAAGAGGACCCACCUGUG -2.2 -2.1 -1.5 1 -1 3 -42.4 52.3 -3.6 2 III 57.9 45.7 61.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0279 NM_003337 Huesken UBE2B 7320 CUCUUGUAACCGCUUGAAAuc UUUCAAGCGGUUACAAGAG -0.9 -2.1 2.3 0 -3 4 -34.6 67.4 -3.4 4 II 42.1 36.2 45.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0280 NM_003337 Huesken UBE2B 7320 UCUUGUAACCGCUUGAAAUcc AUUUCAAGCGGUUACAAGA -1.1 -2.4 2.3 1 1 4 -33.6 83.3 -4 6 II 36.8 58.1 78.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0281 NM_003337 Huesken UBE2B 7320 GUAACCGCUUGAAAUCCCGca CGGGAUUUCAAGCGGUUAC -2.4 -2.2 0.8 0 3 4 -37.5 55.1 -2.6 4 II 52.6 54.8 85.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0282 NM_003969 Huesken UBE2M 9040 GGAGCCGAUGUAGCCACCCcg GGGUGGCUACAUCGGCUCC -3.3 -3.3 -3.5 0 2 4 -45.7 31.7 7.4 0 II 68.4 47.8 58.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0283 NM_003969 Huesken UBE2M 9040 AGCCGAUGUAGCCACCCCGca CGGGGUGGCUACAUCGGCU -2.4 -2.1 -3.5 3 3 5 -45.7 41.5 0.1 2 II 68.4 55.9 54.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0284 NM_003969 Huesken UBE2M 9040 GAUGUAGCCACCCCGCAUGga CAUGCGGGGUGGCUACAUC -2.1 -2.4 -1.8 1 1 6 -43.2 48.8 -2.3 3 II 63.2 47.5 67.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0285 NM_003969 Huesken UBE2M 9040 GCAUGGAGCGCUGCACGUUcu AACGUGCAGCGCUCCAUGC -0.9 -3.4 -1 1 -1 4 -43.1 31.2 -3.3 1 III 63.2 31.5 61.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0286 NM_003969 Huesken UBE2M 9040 UUCUGCUCAAACAGCCGCCgg GGCGGCUGUUUGAGCAGAA -3.3 -0.9 -3 0 4 6 -41.5 65.9 4.8 5 Ib 57.9 72.7 76.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0287 NM_003969 Huesken UBE2M 9040 AACAGCCGCCGGUUGUUCUgc AGAACAACCGGCGGCUGUU -2.1 -0.9 0.8 2 2 8 -41.6 63.6 -1.6 4 II 57.9 49.4 61.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0288 NM_003969 Huesken UBE2M 9040 AGCCGCCGGUUGUUCUGCAgg UGCAGAACAACCGGCGGCU -2.1 -2.1 0 3 1 8 -44 40.3 -1.4 1 II 63.2 35.1 67.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0289 NM_003969 Huesken UBE2M 9040 GCCGCCGGUUGUUCUGCAGga CUGCAGAACAACCGGCGGC -2.1 -3.4 -2.2 0 0 8 -44 42.6 3 -1 II 68.4 27.7 64.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0290 NM_003969 Huesken UBE2M 9040 UGUUCUGCAGGACCUCUGCgg GCAGAGGUCCUGCAGAACA -3.4 -2.1 -5.2 0 3 2 -42.7 69.9 9.8 5 Ib 57.9 64 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0291 NM_003969 Huesken UBE2M 9040 UUCUGCAGGACCUCUGCGGcc CCGCAGAGGUCCUGCAGAA -3.3 -0.9 -5.5 1 4 4 -44.1 61.8 -4.7 5 Ib 63.2 67.6 67.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0292 NM_003969 Huesken UBE2M 9040 CUGCAGGACCUCUGCGGCCuc GGCCGCAGAGGUCCUGCAG -3.3 -2.1 -5.5 0 1 6 -47.5 29.2 5.8 1 II 73.7 49 66.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0293 NM_003969 Huesken UBE2M 9040 UGCAGGACCUCUGCGGCCUcc AGGCCGCAGAGGUCCUGCA -2.1 -2.1 -5.5 1 1 6 -47.5 44.3 -3.3 3 II 68.4 53.3 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0294 NM_003969 Huesken UBE2M 9040 UCUGCGGCCUCCUUGUUCAgu UGAACAAGGAGGCCGCAGA -2.1 -2.4 0.5 1 1 6 -42.9 61.2 -6.1 5 II 57.9 53.1 65.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0295 NM_003969 Huesken UBE2M 9040 CUGCGGCCUCCUUGUUCAGug CUGAACAAGGAGGCCGCAG -2.1 -2.1 0.5 -1 0 6 -42.6 40.7 -1.3 0 II 63.2 35.6 68.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0296 NM_003969 Huesken UBE2M 9040 CUCCUUGUUCAGUGGGUCCuc GGACCCACUGAACAAGGAG -3.3 -2.1 0.2 -1 0 3 -41.4 61 7.7 3 II 57.9 52.3 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0297 NM_003969 Huesken UBE2M 9040 CAGUGGGUCCUCGGGGUUGgg CAACCCCGAGGACCCACUG -2.1 -2.1 -0.3 -1 -1 5 -45 34.2 -4.4 3 II 68.4 42.2 62.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0298 NM_003969 Huesken UBE2M 9040 CUCGGGGUUGGGCUCCAAGaa CUUGGAGCCCAACCCCGAG -2.1 -2.1 -3.2 -1 0 5 -44.9 39.9 2.7 0 II 68.4 42.8 64.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0299 NM_003969 Huesken UBE2M 9040 GGGGUUGGGCUCCAAGAAGag CUUCUUGGAGCCCAACCCC -2.1 -3.3 -0.7 1 -1 4 -43.4 33.8 0.1 1 II 63.2 35.5 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0300 NM_003969 Huesken UBE2M 9040 GGGUUGGGCUCCAAGAAGAga UCUUCUUGGAGCCCAACCC -2.4 -3.3 -0.7 1 -3 4 -42.5 38.2 -11 2 III 57.9 31.3 56.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0301 NM_003969 Huesken UBE2M 9040 GUUGGGCUCCAAGAAGAGAua UCUCUUCUUGGAGCCCAAC -2.4 -2.2 -2.3 1 -1 4 -40.4 38.6 -1.5 1 III 52.6 33.9 69.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0302 NM_003969 Huesken UBE2M 9040 UUGGGCUCCAAGAAGAGAUac AUCUCUUCUUGGAGCCCAA -1.1 -0.9 -2.3 2 1 4 -39.3 65.5 -4.3 5 II 47.4 63.8 77.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0303 NM_003969 Huesken UBE2M 9040 AGAAGAGAUACUGCAGGCCau GGCCUGCAGUAUCUCUUCU -3.3 -2.1 1.5 1 4 4 -40.8 50.9 8.1 6 Ib 52.6 59.8 80.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0304 NM_003969 Huesken UBE2M 9040 UACUGCAGGCCAUAAAUUAug UAAUUUAUGGCCUGCAGUA -1.3 -1.3 1.5 1 -1 4 -34.9 69.4 -6.1 7 II 36.8 56.7 67 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0305 NM_003969 Huesken UBE2M 9040 GGCCAUAAAUUAUGGAGUUua AACUCCAUAAUUUAUGGCC -0.9 -3.3 -2.1 0 -2 4 -33.7 52.9 -1.3 1 III 36.8 32.3 49.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0306 NM_003969 Huesken UBE2M 9040 AAAUUAUGGAGUUUAUCGUaa ACGAUAAACUCCAUAAUUU -2.2 -0.9 1.8 3 4 2 -29.5 94.4 1.4 8 II 26.3 64.4 82.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0307 NM_003969 Huesken UBE2M 9040 UGGAGUUUAUCGUAAGGACug GUCCUUACGAUAAACUCCA -2.2 -2.1 0.7 1 2 2 -35.5 73.4 5.1 5 Ib 42.1 61.6 76.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0308 NM_003969 Huesken UBE2M 9040 GGAGUUUAUCGUAAGGACUgg AGUCCUUACGAUAAACUCC -2.1 -3.3 0.4 1 -1 2 -35.5 64.1 -3.5 3 II 42.1 47.5 60.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0309 NM_003969 Huesken UBE2M 9040 GUUUAUCGUAAGGACUGGCuu GCCAGUCCUUACGAUAAAC -3.4 -2.2 0.4 0 3 3 -36.5 64.2 12.4 5 II 47.4 52.4 68.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0310 NM_003969 Huesken UBE2M 9040 AGGACUGGCUUCCAGUCCUcu AGGACUGGAAGCCAGUCCU -2.1 -2.1 -11.3 2 1 3 -43.8 51.8 -3.9 2 II 57.9 51.2 54.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0311 NM_003969 Huesken UBE2M 9040 AGGAUGUUGAGGCAGACGUug ACGUCUGCCUCAACAUCCU -2.2 -2.1 1.2 3 1 3 -40.8 60.9 -1.6 6 II 52.6 55.3 80.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0312 NM_003969 Huesken UBE2M 9040 UUGAGGCAGACGUUGCCCUcg AGGGCAACGUCUGCCUCAA -2.1 -0.9 -5.7 1 3 4 -42.7 58.5 -4 4 II 57.9 64.3 79.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0313 NM_003969 Huesken UBE2M 9040 CGAGGUCAAUGUUGGGGUGau CACCCCAACAUUGACCUCG -2.1 -2.4 1.8 -2 0 4 -40.4 43.8 1 0 II 57.9 34.4 62.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0314 NM_003969 Huesken UBE2M 9040 GAGGUCAAUGUUGGGGUGAua UCACCCCAACAUUGACCUC -2.4 -2.4 1.7 -1 -2 4 -40.4 44.6 -0.7 4 III 52.6 35.7 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0315 NM_003969 Huesken UBE2M 9040 AAUGUUGGGGUGAUAGACCau GGUCUAUCACCCCAACAUU -3.3 -0.9 -0.8 2 5 4 -38.3 64.3 7.1 6 Ia 47.4 70.1 79.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0316 NM_003969 Huesken UBE2M 9040 UGUUGGGGUGAUAGACCAUug AUGGUCUAUCACCCCAACA -1.1 -2.1 -0.8 -1 1 4 -39.5 53.8 -1.2 6 II 47.4 48.8 71.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0317 NM_003969 Huesken UBE2M 9040 UUGGGGUGAUAGACCAUUGuc CAAUGGUCUAUCACCCCAA -2.1 -0.9 -0.8 1 2 4 -38.2 65.2 -0.3 6 II 47.4 70.2 86.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0318 NM_003969 Huesken UBE2M 9040 GGGGUGAUAGACCAUUGUCuc GACAAUGGUCUAUCACCCC -2.4 -3.3 -1.6 0 0 4 -39.8 53.1 9.8 1 II 52.6 44 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0319 NM_003969 Huesken UBE2M 9040 UAGACCAUUGUCUCACACUuc AGUGUGAGACAAUGGUCUA -2.1 -1.3 -3.1 0 1 2 -37.3 77.7 -6.3 5 II 42.1 70.5 92.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0320 NM_003969 Huesken UBE2M 9040 CAUUGUCUCACACUUCACCuu GGUGAAGUGUGAGACAAUG -3.3 -2.1 0.8 0 2 2 -36.9 75.2 7.8 4 II 47.4 59.4 81.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0321 NM_003969 Huesken UBE2M 9040 CAUGCGGGUAACCCUGGCCca GGCCAGGGUUACCCGCAUG -3.3 -2.1 -2.8 -1 2 5 -45.1 48.1 7.8 2 II 68.4 53.5 73.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0322 NM_003969 Huesken UBE2M 9040 AUGCGGGUAACCCUGGCCCac GGGCCAGGGUUACCCGCAU -3.3 -1.1 -3 2 5 5 -46.3 48.5 7.4 3 II 68.4 64.4 79.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0323 NM_003969 Huesken UBE2M 9040 GCGGGUAACCCUGGCCCACcu GUGGGCCAGGGUUACCCGC -2.2 -3.4 -5.2 0 0 5 -47.4 23.4 8.1 -1 II 73.7 32.8 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0324 NM_003969 Huesken UBE2M 9040 GUAACCCUGGCCCACCUUAaa UAAGGUGGGCCAGGGUUAC -1.3 -2.2 -1.8 1 -2 5 -42.6 48.3 -6.1 2 III 57.9 36.3 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0325 NM_003969 Huesken UBE2M 9040 GCCCACCUUAAAACUGAACac GUUCAGUUUUAAGGUGGGC -2.2 -3.4 -0.4 1 -1 4 -36.5 54.4 9.8 2 II 47.4 36.5 53.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0326 NM_003969 Huesken UBE2M 9040 CCUUAAAACUGAACACAAAcu UUUGUGUUCAGUUUUAAGG -0.9 -3.3 1.1 0 -4 2 -30.4 57.4 -5.6 4 II 31.6 31.7 51.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0327 NM_003969 Huesken UBE2M 9040 ACACAAACUUCCCACUCUUgu AAGAGUGGGAAGUUUGUGU -0.9 -2.2 2 2 1 3 -36.4 52.1 -3.6 5 II 42.1 48.6 85.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0328 NM_003969 Huesken UBE2M 9040 AAACUUCCCACUCUUGUAGaa CUACAAGAGUGGGAAGUUU -2.1 -0.9 -2.5 3 4 3 -35.5 82.6 5.4 6 Ia 42.1 62.1 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0329 NM_003969 Huesken UBE2M 9040 ACUUCCCACUCUUGUAGAAgc UUCUACAAGAGUGGGAAGU -0.9 -2.2 -4.3 1 0 3 -37 65.4 -3.1 3 II 42.1 31.2 68.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0330 NM_003969 Huesken UBE2M 9040 CUUCCCACUCUUGUAGAAGcc CUUCUACAAGAGUGGGAAG -2.1 -2.1 -4.4 0 1 3 -36.9 63.8 3.4 2 II 47.4 48.2 75.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0331 NM_003969 Huesken UBE2M 9040 UCUUGUAGAAGCCCUCAUCag GAUGAGGGCUUCUACAAGA -2.4 -2.4 0.9 0 2 4 -38.6 74.7 7.5 7 Ia 47.4 66.8 82.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0332 NM_003969 Huesken UBE2M 9040 UGUAGAAGCCCUCAUCAGGac CCUGAUGAGGGCUUCUACA -3.3 -2.1 -1.8 1 3 4 -40.7 62 3.1 5 Ia 52.6 63.2 77.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0333 NM_003969 Huesken UBE2M 9040 UAGAAGCCCUCAUCAGGACag GUCCUGAUGAGGGCUUCUA -2.2 -1.3 -5.7 1 3 4 -41 58.9 7.8 5 Ib 52.6 59.8 80.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0334 NM_003969 Huesken UBE2M 9040 CCCUCAUCAGGACAGAUGAcc UCAUCUGUCCUGAUGAGGG -2.4 -3.3 -4.9 0 -4 3 -41 52.8 -3.4 2 III 52.6 32.5 57.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0335 NM_003969 Huesken UBE2M 9040 CCUCAUCAGGACAGAUGACca GUCAUCUGUCCUGAUGAGG -2.2 -3.3 -5.1 0 0 2 -39.9 40.9 5.5 1 II 52.6 34.3 58.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0336 NM_003969 Huesken UBE2M 9040 CAUCAGGACAGAUGACCAGcu CUGGUCAUCUGUCCUGAUG -2.1 -2.1 -2.3 0 1 2 -39.6 46.4 0.7 4 II 52.6 45.3 76.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0337 NM_003969 Huesken UBE2M 9040 ACAGAUGACCAGCUUGAAGuu CUUCAAGCUGGUCAUCUGU -2.1 -2.2 1.6 2 3 2 -38 60.2 9.7 5 Ib 47.4 53 77 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0338 NM_003969 Huesken UBE2M 9040 GUCGUCUGGAUCUGAGAAGcu CUUCUCAGAUCCAGACGAC -2.1 -2.2 1.1 1 0 2 -39.1 53.8 -2.4 4 II 52.6 43.2 65.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0339 NM_003969 Huesken UBE2M 9040 GUCUGGAUCUGAGAAGCUGau CAGCUUCUCAGAUCCAGAC -2.1 -2.2 1.1 1 1 2 -39.7 47.5 0 3 II 52.6 44.7 79.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0340 NM_003969 Huesken UBE2M 9040 GAUCUGAGAAGCUGAUAUCac GAUAUCAGCUUCUCAGAUC -2.4 -2.4 0.9 0 1 2 -35.9 65.3 5.1 5 II 42.1 49.4 60.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0341 NM_003969 Huesken UBE2M 9040 UCUGAGAAGCUGAUAUCACac GUGAUAUCAGCUUCUCAGA -2.2 -2.4 0.9 1 4 2 -36.7 60.4 9.8 6 Ib 42.1 63.4 70.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0342 NM_003969 Huesken UBE2M 9040 GUCUUGGGCAGGUUCAGCUcg AGCUGAACCUGCCCAAGAC -2.1 -2.2 -0.5 1 1 4 -42.4 61.1 -1.6 4 III 57.9 47.2 71.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0343 NM_003969 Huesken UBE2M 9040 CUUGGGCAGGUUCAGCUCGuu CGAGCUGAACCUGCCCAAG -2.4 -2.1 -0.5 0 1 4 -42.6 43.2 3.4 2 II 63.2 51.8 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0344 NM_003969 Huesken UBE2M 9040 UUGGGCAGGUUCAGCUCGUuu ACGAGCUGAACCUGCCCAA -2.2 -0.9 -0.5 0 2 4 -42.7 42.3 -8.9 4 II 57.9 57.6 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0345 NM_003969 Huesken UBE2M 9040 CGUUUAUGUCCUUCUGGAUcc AUCCAGAAGGACAUAAACG -1.1 -2.4 -1.9 0 -2 2 -35.2 71 -5.3 3 II 42.1 34.8 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0346 NM_003969 Huesken UBE2M 9040 GAUCCGCAGCUGCGCCGCCga GGCGGCGCAGCUGCGGAUC -3.3 -2.4 -6.3 1 3 8 -48.4 24.7 9.8 0 II 78.9 38.7 71.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0347 NM_003969 Huesken UBE2M 9040 AUCCGCAGCUGCGCCGCCGac CGGCGGCGCAGCUGCGGAU -2.4 -1.1 -6.3 3 4 9 -48.4 33.5 -2.4 2 II 78.9 54.9 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0348 NM_003969 Huesken UBE2M 9040 AGCUGCGCCGCCGACGCCUuc AGGCGUCGGCGGCGCAGCU -2.1 -2.1 -6.1 2 1 9 -49.5 27.6 -8.7 2 II 78.9 43.7 51.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0349 NM_003969 Huesken UBE2M 9040 CCGACGCCUUCUUGCUGCUgc AGCAGCAAGAAGGCGUCGG -2.1 -3.3 -1.3 -2 -2 4 -43 41.9 -5.3 -1 III 63.2 30.2 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0350 NM_003969 Huesken UBE2M 9040 GACGCCUUCUUGCUGCUGCcc GCAGCAGCAAGAAGGCGUC -3.4 -2.4 -1.3 2 2 4 -42.8 60.3 12.1 1 II 63.2 48.4 61 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0351 NM_003969 Huesken UBE2M 9040 CGCCUUCUUGCUGCUGCCCuu GGGCAGCAGCAAGAAGGCG -3.3 -2.4 -1.3 0 0 4 -44.8 45.7 6.1 -1 II 68.4 42.9 58.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0352 NM_003969 Huesken UBE2M 9040 GCUGCCCUUGGUGCCGCCCgc GGGCGGCACCAAGGGCAGC -3.3 -3.4 -2 0 2 7 -49.4 36.4 10.4 -1 II 78.9 38.2 64.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0353 NM_003969 Huesken UBE2M 9040 UUGGUGCCGCCCGCCGACUcc AGUCGGCGGGCGGCACCAA -2.1 -0.9 -4.1 1 1 11 -47.9 36.2 -8.7 3 II 73.7 56.2 73.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0354 NM_003969 Huesken UBE2M 9040 UGGUGCCGCCCGCCGACUCcu GAGUCGGCGGGCGGCACCA -2.4 -2.1 -4.1 1 2 11 -49.4 39.2 7.5 2 II 78.9 51.5 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0355 NM_003969 Huesken UBE2M 9040 UGCCGCCCGCCGACUCCUCcu GAGGAGUCGGCGGGCGGCA -2.4 -2.1 -4.1 2 2 11 -49.6 31.2 2.5 1 II 78.9 48.6 59.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0356 NM_003969 Huesken UBE2M 9040 CCCGCCGACUCCUCCUCCUuc AGGAGGAGGAGUCGGCGGG -2.1 -3.3 1.3 0 -2 7 -48.2 35 -10.7 0 III 73.7 33 41.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0357 NM_003969 Huesken UBE2M 9040 GACUCCUCCUCCUUCUUCUgc AGAAGAAGGAGGAGGAGUC -2.1 -2.4 3 2 0 2 -40.9 75.3 -6.3 4 III 52.6 44.7 59.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0358 XM_371822 Huesken C6orf110 55362 ACUGGAAGUCUGUGUCCGUga ACGGACACAGACUUCCAGU -2.2 -2.2 -2.3 0 2 3 -40.7 42 -4 3 II 52.6 43.8 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0359 XM_371822 Huesken C6orf110 55362 GUCUGUGUCCGUGAGGGCGuc CGCCCUCACGGACACAGAC -2.4 -2.2 -0.5 1 2 5 -44.6 47.7 3 2 II 68.4 46.3 59.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0360 XM_371822 Huesken C6orf110 55362 CUCAUCUUGGGAUGAGGAUga AUCCUCAUCCCAAGAUGAG -1.1 -2.1 -5.8 0 -2 3 -38.7 59.6 -6 3 II 47.4 37.1 53.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0361 XM_371822 Huesken C6orf110 55362 GGGGCUCAUCCCCUGAGCUcc AGCUCAGGGGAUGAGCCCC -2.1 -3.3 -6.5 0 0 5 -47.5 38.9 -3.9 -2 III 68.4 32 43 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0362 XM_371822 Huesken C6orf110 55362 CCUGAGCUCCCAGGAGCCCca GGGCUCCUGGGAGCUCAGG -3.3 -3.3 -10.5 -1 1 4 -48.5 20.1 5.8 0 II 73.7 37.3 36.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0363 XM_371822 Huesken C6orf110 55362 CUCCCAGGAGCCCCAUCCCca GGGAUGGGGCUCCUGGGAG -3.3 -2.1 -2.9 0 1 5 -48.6 34.6 3.1 0 II 73.7 44.9 43.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0364 XM_371822 Huesken C6orf110 55362 CAUCCCCGUCCACCUCUGAgu UCAGAGGUGGACGGGGAUG -2.4 -2.1 1.5 0 -2 5 -44.5 43 -5.7 2 III 63.2 31.4 29.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0365 XM_371822 Huesken C6orf110 55362 UCUGAGUCCUGCAGCACCUga AGGUGCUGCAGGACUCAGA -2.1 -2.4 -0.1 1 2 2 -43.9 49.4 -6.2 5 II 57.9 58.4 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0366 XM_371822 Huesken C6orf110 55362 AUUUCGCAGAUUUGGGGACag GUCCCCAAAUCUGCGAAAU -2.2 -1.1 2.3 1 4 4 -37.2 68.5 10.4 6 Ib 47.4 55 82 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0367 XM_371822 Huesken C6orf110 55362 UUGCUUCUGGGGUCCACAGua CUGUGGACCCCAGAAGCAA -2.1 -0.9 -0.4 2 3 4 -42.3 65.2 0 4 Ib 57.9 63.6 75.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0368 XM_371822 Huesken C6orf110 55362 UCUUGUAGUUGUGGGCACUga AGUGCCCACAACUACAAGA -2.1 -2.4 0 -1 1 4 -39 62.7 -1 6 II 47.4 54.7 81.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0369 XM_371822 Huesken C6orf110 55362 CACUGAGGUAUUUGAAGUGuc CACUUCAAAUACCUCAGUG -2.1 -2.1 0.1 -2 0 2 -34.5 59.8 1 4 II 42.1 47 55 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0370 XM_371822 Huesken C6orf110 55362 CAGACGUGGCAGAGACAGAug UCUGUCUCUGCCACGUCUG -2.4 -2.1 1.9 0 -3 3 -42.1 38.8 -6 2 III 57.9 35.7 68.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0371 XM_371822 Huesken C6orf110 55362 ACAUAGACGUGGGAGCUAGga CUAGCUCCCACGUCUAUGU -2.1 -2.2 1.6 2 2 3 -40.1 48.8 2.7 7 Ia 52.6 49.8 66.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0372 XM_371822 Huesken C6orf110 55362 AUAGACGUGGGAGCUAGGAac UCCUAGCUCCCACGUCUAU -2.4 -1.1 1.6 2 2 3 -41.5 45.5 -1.1 6 II 52.6 49.9 79.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0373 XM_371822 Huesken C6orf110 55362 ACGUGGGAGCUAGGAACCCcg GGGUUCCUAGCUCCCACGU -3.3 -2.2 -3.4 1 3 3 -44.3 27.3 7.4 2 II 63.2 51.2 57.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0374 XM_371822 Huesken C6orf110 55362 CAGAAGAGGCAGAGGAUGGgc CCAUCCUCUGCCUCUUCUG -3.3 -2.1 2.5 -1 0 3 -41.7 43.4 0.4 4 II 57.9 49.3 53.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0375 XM_371822 Huesken C6orf110 55362 CUUCUUGUCCAGCUUGGCCgg GGCCAAGCUGGACAAGAAG -3.3 -2.1 -0.8 1 3 4 -41.1 67.4 12.4 3 II 57.9 57.4 65 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0376 XM_371822 Huesken C6orf110 55362 UGUCCAGCUUGGCCGGCAGgu CUGCCGGCCAAGCUGGACA -2.1 -2.1 -5.8 1 3 7 -46 46.8 2.4 3 II 68.4 48.6 65.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0377 XM_371822 Huesken C6orf110 55362 CUACCAGGUGCUUCAGCAGca CUGCUGAAGCACCUGGUAG -2.1 -2.1 -2 0 1 2 -41.3 48.1 -1.3 1 II 57.9 44.5 75 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0378 XM_371822 Huesken C6orf110 55362 UACCAGGUGCUUCAGCAGCau GCUGCUGAAGCACCUGGUA -3.4 -1.3 -3 2 3 2 -42.6 55.5 15.5 4 II 57.9 67 82.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0379 XM_371822 Huesken C6orf110 55362 AUGACCACCGUGAAGACGCac GCGUCUUCACGGUGGUCAU -3.4 -1.1 -0.6 2 4 3 -41.2 57.5 4.8 4 Ib 57.9 69.3 75.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0380 XM_371822 Huesken C6orf110 55362 GCGUAGGCUGCGCCAAACUgg AGUUUGGCGCAGCCUACGC -2.1 -3.4 -2.2 0 -2 5 -43 35 -1.2 1 III 63.2 34.5 60.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0381 XM_371822 Huesken C6orf110 55362 UGAUGCCGCUUCACGUUGCgc GCAACGUGAAGCGGCAUCA -3.4 -2.1 -1 1 3 5 -40.9 58.4 2.5 4 II 57.9 61.2 72.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0382 XM_371822 Huesken C6orf110 55362 GCUUCACGUUGCGCCUCUCgg GAGAGGCGCAACGUGAAGC -2.4 -3.4 0.2 0 1 5 -42.2 43.3 5.1 1 II 63.2 32 56.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0383 XM_371822 Huesken C6orf110 55362 UUGCGCCUCUCGGCGGCCGag CGGCCGCCGAGAGGCGCAA -2.4 -0.9 -8.4 2 4 9 -48.4 37.2 -2.4 2 II 78.9 58.6 72.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0384 XM_371822 Huesken C6orf110 55362 GGAUCAUGUACAUGAGCAGgc CUGCUCAUGUACAUGAUCC -2.1 -3.3 -1.4 0 1 2 -37.6 54.5 -2.4 3 II 47.4 38.7 49 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0385 XM_371822 Huesken C6orf110 55362 UCAUGUACAUGAGCAGGCCug GGCCUGCUCAUGUACAUGA -3.3 -2.4 -0.8 0 4 4 -40.8 57.9 7.4 6 Ia 52.6 65.3 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0386 XM_371822 Huesken C6orf110 55362 AGCAGGUCCAUGGCGUUGCcg GCAACGCCAUGGACCUGCU -3.4 -2.1 -0.5 3 2 4 -43.9 52.8 7.4 5 II 63.2 58.4 71.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0387 XM_371822 Huesken C6orf110 55362 UCCAUGGCGUUGCCGAUAAag UUAUCGGCAACGCCAUGGA -0.9 -2.4 -3 1 -2 4 -40.1 54.1 -1.4 6 II 52.6 44.9 62.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0388 XM_371822 Huesken C6orf110 55362 GAAAGUGUAGCACUUGUGCau GCACAAGUGCUACACUUUC -3.4 -2.4 -2.6 0 3 2 -36.7 66.4 9.8 4 II 47.4 55.4 83.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0389 XM_371822 Huesken C6orf110 55362 AAAGUGUAGCACUUGUGCAug UGCACAAGUGCUACACUUU -2.1 -0.9 -2.6 3 3 2 -36.4 71.4 -1.5 5 II 42.1 59.2 99.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0390 XM_371822 Huesken C6orf110 55362 GGAGGGCCGAGAAGCACCAca UGGUGCUUCUCGGCCCUCC -2.1 -3.3 -1.3 0 -1 6 -46.5 18.7 -6.3 0 III 68.4 30.4 65.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0391 XM_371822 Huesken C6orf110 55362 GGUGGGGAAGAACUGGGUGau CACCCAGUUCUUCCCCACC -2.1 -3.3 2.3 0 2 4 -43.5 37 7 1 II 63.2 37.4 56.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0392 XM_371822 Huesken C6orf110 55362 UCCAUGGUGGUGAUGAUGAug UCAUCAUCACCACCAUGGA -2.4 -2.4 -1.1 1 0 2 -39.8 62 -4 6 II 47.4 56.3 79.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0393 XM_371822 Huesken C6orf110 55362 CCAUGGUGGUGAUGAUGAUgg AUCAUCAUCACCACCAUGG -1.1 -3.3 0 0 -2 2 -38.5 44.5 -6 3 III 47.4 27.7 59.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0394 XM_371822 Huesken C6orf110 55362 AUGAUGAUGGCUGGAGUGGug CCACUCCAGCCAUCAUCAU -3.3 -1.1 4.6 1 3 3 -40.7 56.1 0.7 7 Ia 52.6 60.2 77.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0395 XM_371822 Huesken C6orf110 55362 GAUGAUGGCUGGAGUGGUGag CACCACUCCAGCCAUCAUC -2.1 -2.4 0 2 3 -41.8 42.5 0.1 3 II 57.9 40 70.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0396 XM_371822 Huesken C6orf110 55362 UGGUGAGGAAGAAGAGGAGga CUCCUCUUCUUCCUCACCA -2.1 -2.1 -1 2 2 -40.6 44.9 -2.6 6 II 52.6 50.1 68 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0397 XM_371822 Huesken C6orf110 55362 AGGAGGAUGAAGAGGACGAca UCGUCCUCUUCAUCCUCCU -2.4 -2.1 4.5 1 0 2 -41.4 44.9 -4 5 II 52.6 46.7 55.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0398 XM_371822 Huesken C6orf110 55362 AGAUGAAGCCUCGGAUGGAga UCCAUCCGAGGCUUCAUCU -2.4 -2.1 0.1 1 1 3 -41.3 35.8 -6.1 5 II 52.6 38.5 65.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0399 XM_371822 Huesken C6orf110 55362 GGCGUGGCUCCCCACGGCAgg UGCCGUGGGGAGCCACGCC -2.1 -3.3 -8 0 -2 4 -50 19.5 -6.1 0 III 78.9 27.3 62.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0400 XM_371822 Huesken C6orf110 55362 AUUUACACACGUUGAAGUCcu GACUUCAACGUGUGUAAAU -2.4 -1.1 0.8 0 4 2 -32.6 80.3 13.1 7 Ia 36.8 61.5 101.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0401 XM_371822 Huesken C6orf110 55362 CACGUUGAAGUCCUUCAGGau CCUGAAGGACUUCAACGUG -3.3 -2.1 -1.4 -1 1 2 -38.1 58.7 0.4 2 II 52.6 53 84.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0402 XM_371822 Huesken C6orf110 55362 AUAGUCUCAUUGUGGAAGGug CCUUCCACAAUGAGACUAU -3.3 -1.1 1.1 1 4 2 -36.1 70.7 0 6 Ia 42.1 65 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0403 XM_371822 Huesken C6orf110 55362 UUGUGGAAGGUGACAAAGGcc CCUUUGUCACCUUCCACAA -3.3 -0.9 0.6 1 3 2 -37.5 59 -2.6 6 Ib 47.4 72.8 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0404 XM_371822 Huesken C6orf110 55362 UCAAUGGCCUCCACCUGCUca AGCAGGUGGAGGCCAUUGA -2.1 -2.4 -2.4 1 2 4 -43.7 52.8 -11.3 5 II 57.9 60.6 77.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0405 XM_371822 Huesken C6orf110 55362 CCACCUGCUCACAGCCUCGca CGAGGCUGUGAGCAGGUGG -2.4 -3.3 -2.3 -1 0 3 -45.1 37.6 -4.6 1 II 68.4 46.2 42.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0406 XM_371822 Huesken C6orf110 55362 UGAUCAUGGUAGGCACGUUcu AACGUGCCUACCAUGAUCA -0.9 -2.1 -1.6 2 1 3 -38.7 58.5 -1.7 5 II 47.4 50.5 80.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0407 XM_371822 Huesken C6orf110 55362 GGAGGUUUGUGAAGUACAGcu CUGUACUUCACAAACCUCC -2.1 -3.3 0.6 1 1 2 -36.8 48.8 -2.6 2 II 47.4 39.5 57.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0408 XM_371822 Huesken C6orf110 55362 CUCGGCCUUCUUCCUCUCUgc AGAGAGGAAGAAGGCCGAG -2.1 -2.1 -0.6 -1 -2 5 -42.1 53.5 -0.6 1 III 57.9 41.6 49.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0409 XM_371822 Huesken C6orf110 55362 CUUCUUCCUCUCUGCAUCGag CGAUGCAGAGAGGAAGAAG -2.4 -2.1 -1 1 2 -38.7 62.7 -4.4 4 II 52.6 55.2 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0410 XM_371822 Huesken C6orf110 55362 AUCGAGGAACAUUAGGCGAgc UCGCCUAAUGUUCCUCGAU -2.4 -1.1 1.3 1 1 4 -38.2 56.1 4.3 5 II 47.4 49.8 77.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0411 XM_371822 Huesken C6orf110 55362 CGAGCCACGUUGUAACACGgg CGUGUUACAACGUGGCUCG -2.4 -2.4 -1.7 0 0 3 -38.8 46.1 -2 0 II 57.9 49 91.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0412 XM_371822 Huesken C6orf110 55362 AGCCACGUUGUAACACGGGcg CCCGUGUUACAACGUGGCU -3.3 -2.1 -2.4 2 3 4 -40.6 40.8 0.1 2 II 57.9 52.2 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0413 XM_371822 Huesken C6orf110 55362 UGUGCAGUUGGGGUAGGCUuc AGCCUACCCCAACUGCACA -2.1 -2.1 0.5 0 3 4 -43.5 52.2 -1.6 4 II 57.9 53 70.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0414 XM_371822 Huesken C6orf110 55362 CAAAAUGCUUCUUGAUCUUuu AAGAUCAAGAAGCAUUUUG -0.9 -2.1 0.3 -2 -1 2 -30.8 70.1 -2.6 5 II 31.6 45.9 61.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0415 XM_371822 Huesken C6orf110 55362 GCAUAUUUGGAGAUUCCAUug AUGGAAUCUCCAAAUAUGC -1.1 -3.4 -2.5 2 0 2 -34 69.5 0.8 3 II 36.8 41 78.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0416 XM_371822 Huesken C6orf110 55362 GAUCAUCCUCCUUGUAGCGca CGCUACAAGGAGGAUGAUC -2.4 -2.4 1.2 0 3 3 -39.1 58.9 3.4 3 II 52.6 45.6 79.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0417 XM_371822 Huesken C6orf110 55362 UGGAGGUGUGUCUACGCAUgc AUGCGUAGACACACCUCCA -1.1 -2.1 1.1 1 0 3 -41 54.2 -6.3 5 II 52.6 56.6 76.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0418 XM_371822 Huesken C6orf110 55362 GACGGUGAGCAGCAGAUACag GUAUCUGCUGCUCACCGUC -2.2 -2.4 0.6 1 0 3 -41.3 47.5 12.1 2 II 57.9 42.3 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0419 XM_371822 Huesken C6orf110 55362 GUUGUUCCCUGAUUUCAAGuu CUUGAAAUCAGGGAACAAC -2.1 -2.2 -2.6 1 2 3 -34.3 74.5 2.3 2 II 42.1 46.2 71.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0420 XM_371822 Huesken C6orf110 55362 AUGGUGGUUCUCCCAAAGCug GCUUUGGGAGAACCACCAU -3.4 -1.1 -2.5 1 3 3 -40.1 57 7.5 4 II 52.6 65.5 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0421 XM_371822 Huesken C6orf110 55362 GUUCUCCCAAAGCUGUAGGca CCUACAGCUUUGGGAGAAC -3.3 -2.2 -2.3 1 3 3 -39.1 68.4 7 3 II 52.6 48.1 81.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0422 XM_371822 Huesken C6orf110 55362 GCACGAUGCCUACGGAGAGga CUCUCCGUAGGCAUCGUGC -2.1 -3.4 0.4 2 1 3 -42.7 27.4 2.4 1 II 63.2 31.9 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0423 XM_371822 Huesken C6orf110 55362 CAGCAGCCCGAUGAUGUGCcg GCACAUCAUCGGGCUGCUG -3.4 -2.1 -0.3 1 0 5 -43.1 44.6 13.4 2 II 63.2 47.2 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0424 XM_371822 Huesken C6orf110 55362 AAGGACAGGUAGUGCACGGca CCGUGCACUACCUGUCCUU -3.3 -0.9 1 1 4 3 -41.7 48.5 5 4 Ib 57.9 56.6 86.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0425 XM_371822 Huesken C6orf110 55362 GUCCCGGAUCUCAUCAUCCuu GGAUGAUGAGAUCCGGGAC -3.3 -2.2 -3.8 1 2 5 -41.8 52.3 4.8 1 II 57.9 54.8 89.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0426 XM_371822 Huesken C6orf110 55362 CGGAUCUCAUCAUCCUUUAuc UAAAGGAUGAUGAGAUCCG -1.3 -2.4 -4 0 -5 3 -35.8 67.5 -8.1 3 III 42.1 36.8 24.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0427 XM_371822 Huesken C6orf110 55362 UGUCCCUUUGGUCAAAGUCaa GACUUUGACCAAAGGGACA -2.4 -2.1 -1.3 2 3 3 -37.8 76.3 12.8 4 II 47.4 65.1 89.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0428 XM_371822 Huesken C6orf110 55362 UUGGUCAAAGUCAACGGAGcu CUCCGUUGACUUUGACCAA -2.1 -0.9 0.1 0 3 3 -36.9 60.8 -4.9 6 Ib 47.4 69.6 98.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0429 XM_371822 Huesken C6orf110 55362 AGUCAACGGAGCUGGAGACag GUCUCCAGCUCCGUUGACU -2.2 -2.1 -1.1 2 3 3 -42.1 45.7 7.8 3 Ib 57.9 42.7 69.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0430 XM_371822 Huesken C6orf110 55362 CUGGAGACAGAGGUGAGACgc GUCUCACCUCUGUCUCCAG -2.2 -2.1 0.3 -1 1 2 -42 46.4 12.7 2 II 57.9 48.5 88.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0431 XM_371822 Huesken C6orf110 55362 UGAGACGCUCAUACCGGUCau GACCGGUAUGAGCGUCUCA -2.4 -2.1 -0.7 0 3 4 -41.8 55.6 12.8 5 II 57.9 63.8 99 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0432 XM_371822 Huesken C6orf110 55362 UCAUACCGGUCAUGGCUGUcc ACAGCCAUGACCGGUAUGA -2.2 -2.4 -2.4 0 1 4 -41.1 51.5 -3.6 6 II 52.6 46.8 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0433 XM_371822 Huesken C6orf110 55362 GGCUGUCCCCGUGCAUAGCug GCUAUGCACGGGGACAGCC -3.4 -3.3 0.1 1 0 5 -45.5 44.2 10.4 0 II 68.4 33.5 73.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0434 XM_371822 Huesken C6orf110 55362 GGAAGUCUGUGUCCGUGAGgg CUCACGGACACAGACUUCC -2.1 -3.3 -0.6 1 1 3 -40.9 52.6 5.4 1 II 57.9 32.7 61.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0435 XM_371822 Huesken C6orf110 55362 GUGAGGGCGUCGGGUGGCAuc UGCCACCCGACGCCCUCAC -2.1 -2.2 0.5 0 -1 5 -47.9 16.8 -6.1 2 III 73.7 26.6 12.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0436 XM_371822 Huesken C6orf110 55362 CGUCGGGUGGCAUCAGCAAcu UUGCUGAUGCCACCCGACG -0.9 -2.4 -0.6 1 -3 4 -43.2 29.1 -8.1 1 III 63.2 25.4 39.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0437 XM_371822 Huesken C6orf110 55362 AACUCCUCAUCUUGGGAUGag CAUCCCAAGAUGAGGAGUU -2.1 -0.9 -2.1 1 2 3 -38.3 75.2 0.7 4 Ib 47.4 53 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0438 XM_371822 Huesken C6orf110 55362 AUCCCCUGAGCUCCCAGGAgc UCCUGGGAGCUCAGGGGAU -2.4 -1.1 -6.3 3 1 4 -46.5 52.1 -0.7 2 II 63.2 46.1 52 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0439 XM_371822 Huesken C6orf110 55362 GUCCUGCAGCACCUGAGCGau CGCUCAGGUGCUGCAGGAC -2.4 -2.2 -1.5 2 3 3 -45.2 43.7 4.7 0 II 68.4 43.7 46.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0440 XM_371822 Huesken C6orf110 55362 CCUGAGCGAUGUAUUUCGCag GCGAAAUACAUCGCUCAGG -3.4 -3.3 -4.3 -1 2 3 -38 53.4 10.9 1 II 52.6 41.8 40.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0441 XM_371822 Huesken C6orf110 55362 AGCGAUGUAUUUCGCAGAUuu AUCUGCGAAAUACAUCGCU -1.1 -2.1 -4.3 0 0 3 -35.8 56.8 4.2 3 II 42.1 40.2 50.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0442 XM_371822 Huesken C6orf110 55362 UUCUGGGGUCCACAGUAUCug GAUACUGUGGACCCCAGAA -2.4 -0.9 -0.9 0 2 4 -40.8 58.1 7.5 6 II 52.6 64.8 73.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0443 XM_371822 Huesken C6orf110 55362 AGUUGUGGGCACUGAGGUAuu UACCUCAGUGCCCACAACU -1.3 -2.1 0.3 1 0 4 -41.4 47.8 -3.8 5 II 52.6 36.4 51.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0444 XM_371822 Huesken C6orf110 55362 UGACGAUGGUGAUGACCAGga CUGGUCAUCACCAUCGUCA -2.1 -2.1 -2.3 2 3 2 -40 46.4 0 4 Ib 52.6 51.4 67 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0445 XM_371822 Huesken C6orf110 55362 CGUGCGCAUGGUGGAAAAGaa CUUUUCCACCAUGCGCACG -2.1 -2.4 2.8 -2 -1 4 -39.3 38.3 1 0 II 57.9 31.1 0 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0446 XM_371822 Huesken C6orf110 55362 GCGCAUGGUGGAAAAGAAGag CUUCUUUUCCACCAUGCGC -2.1 -3.4 3.1 1 -1 4 -38 36.1 0.1 2 II 52.6 36.6 39.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0447 XM_371822 Huesken C6orf110 55362 GAGGAUGGGCGCGGCCACCac GGUGGCCGCGCCCAUCCUC -3.3 -2.4 -4.4 0 1 10 -49.2 21.4 7.8 1 II 78.9 42.3 49.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0448 XM_371822 Huesken C6orf110 55362 GGAUGGGCGCGGCCACCACcu GUGGUGGCCGCGCCCAUCC -2.2 -3.3 -4.4 1 1 10 -49 23.9 9.8 1 II 78.9 31.9 46.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0449 XM_371822 Huesken C6orf110 55362 GGCGCGGCCACCACCUGGUuc ACCAGGUGGUGGCCGCGCC -2.2 -3.3 -3.2 1 -1 9 -49.8 25.3 -11.3 0 III 78.9 31.1 57.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0450 XM_371822 Huesken C6orf110 55362 GCAGGUAGGCGUAGUAGAGau CUCUACUACGCCUACCUGC -2.1 -3.4 0.9 0 1 4 -41.3 37.2 0.4 1 II 57.9 34.7 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0451 XM_371822 Huesken C6orf110 55362 ACGAUGAUGGGGCAGGUGAua UCACCUGCCCCAUCAUCGU -2.4 -2.2 2.6 2 -1 5 -43.3 48.4 -1.4 5 II 57.9 45.1 73 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0452 XM_371822 Huesken C6orf110 55362 GGUGAUACUGUAGGUCAUGac CAUGACCUACAGUAUCACC -2.1 -3.3 1.5 -1 0 2 -37.6 45.1 2.7 3 II 47.4 42.7 58.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0453 XM_371822 Huesken C6orf110 55362 GUGAUACUGUAGGUCAUGAcc UCAUGACCUACAGUAUCAC -2.4 -2.2 1.5 1 -1 2 -36.7 62.4 0.9 4 II 42.1 37.1 60.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0454 XM_371822 Huesken C6orf110 55362 ACAUCAUCCAGGCGUAGGCug GCCUACGCCUGGAUGAUGU -3.4 -2.2 -0.7 2 4 4 -42.3 58.8 9.8 5 Ia 57.9 55.1 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0455 XM_371822 Huesken C6orf110 55362 CCGCUUCACGUUGCGCCUCuc GAGGCGCAACGUGAAGCGG -2.4 -3.3 -3.2 1 -1 5 -43.4 37.3 8.4 -1 II 68.4 41.4 59.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0456 XM_371822 Huesken C6orf110 55362 CGCUUCACGUUGCGCCUCUcg AGAGGCGCAACGUGAAGCG -2.1 -2.4 -1.9 -1 -3 5 -42.2 43.9 -3.6 2 III 63.2 34.9 35.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0457 XM_371822 Huesken C6orf110 55362 ACGUUGCGCCUCUCGGCGGcc CCGCCGAGAGGCGCAACGU -3.3 -2.2 -8.4 2 3 6 -46.1 40.5 -2.4 2 II 73.7 49.1 21.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0458 XM_371822 Huesken C6orf110 55362 GCAGAGCCGGAUCAUGUACau GUACAUGAUCCGGCUCUGC -2.2 -3.4 1.5 1 0 5 -41.4 43.6 17.8 2 II 57.9 36.4 46.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0459 XM_371822 Huesken C6orf110 55362 GAUCAUGUACAUGAGCAGGcc CCUGCUCAUGUACAUGAUC -3.3 -2.4 -1.4 1 2 2 -37.6 61.2 8 3 II 47.4 50.1 73.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0460 XM_371822 Huesken C6orf110 55362 AUGUACAUGAGCAGGCCUGgg CAGGCCUGCUCAUGUACAU -2.1 -1.1 0 1 3 4 -40.5 58.8 -2.2 7 Ia 52.6 61.2 72.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0461 XM_371822 Huesken C6orf110 55362 UGAGCAGGCCUGGGAUGCGca CGCAUCCCAGGCCUGCUCA -2.4 -2.1 -0.9 0 4 4 -46.4 31.5 0 4 II 68.4 54.6 74.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0462 XM_371822 Huesken C6orf110 55362 GCAGCAGGUCCAUGGCGUUgc AACGCCAUGGACCUGCUGC -0.9 -3.4 0.7 -1 -1 4 -43.9 25.3 -6.3 1 III 63.2 24.8 27.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0463 XM_371822 Huesken C6orf110 55362 CCAUGGCGUUGCCGAUAAAgg UUUAUCGGCAACGCCAUGG -0.9 -3.3 -3 -2 -4 4 -38.6 34.5 -5.7 1 III 52.6 18 36.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0464 XM_371822 Huesken C6orf110 55362 ACCAUGAAGAUGAGGAAAGug CUUUCCUCAUCUUCAUGGU -2.1 -2.2 0.5 1 1 2 -35.9 56.4 -2.6 6 Ib 42.1 54.1 72.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0465 XM_371822 Huesken C6orf110 55362 CUUGUGCAUGGUUGUCCUGuu CAGGACAACCAUGCACAAG -2.1 -2.1 -0.7 -2 1 2 -38.7 56.3 1 3 II 52.6 46.4 61.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0466 XM_371822 Huesken C6orf110 55362 AUGGUUGUCCUGUUCUCCCca GGGAGAACAGGACAACCAU -3.3 -1.1 -0.7 2 5 3 -40.4 72.5 9.7 5 Ib 52.6 72.6 65.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0467 XM_371822 Huesken C6orf110 55362 UUGUCCUGUUCUCCCCAGAgc UCUGGGGAGAACAGGACAA -2.4 -0.9 -2.5 1 0 4 -41.6 70.4 -0.7 5 II 52.6 57.4 68 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0468 XM_371822 Huesken C6orf110 55362 CCUGUUCUCCCCAGAGCGUgu ACGCUCUGGGGAGAACAGG -2.2 -3.3 -2.1 -1 -1 4 -44.1 36 -13.3 0 III 63.2 32.6 48.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0469 XM_371822 Huesken C6orf110 55362 AGCACCACAGCAGCAGGGUgg ACCCUGCUGCUGUGGUGCU -2.2 -2.1 -1.6 1 1 3 -45.6 40 -6.3 2 II 63.2 41.5 58.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0470 XM_371822 Huesken C6orf110 55362 AGAACUGGGUGAUGAUGGGgu CCCAUCAUCACCCAGUUCU -3.3 -2.1 3.6 1 4 3 -40.5 52.4 0 5 Ib 52.6 50 68.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0471 XM_371822 Huesken C6orf110 55362 AACUUGUCCAUGGUGGUGAug UCACCACCAUGGACAAGUU -2.4 -0.9 -1.1 3 1 2 -39 70.5 -1.4 7 II 47.4 56.1 67.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0472 XM_371822 Huesken C6orf110 55362 GUGGUGAUGAUGAUGGCUGga CAGCCAUCAUCAUCACCAC -2.1 -2.2 4.5 1 2 3 -39.6 55.1 -0.3 4 II 52.6 55.5 74.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0473 XM_371822 Huesken C6orf110 55362 AAGAAGAGGAGGAUGAAGAgg UCUUCAUCCUCCUCUUCUU -2.4 -0.9 2 1 2 -37.4 62.5 -1.3 7 II 42.1 57.3 58.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0474 XM_371822 Huesken C6orf110 55362 UGAAGAGGACGACAUUGAUga AUCAAUGUCGUCCUCUUCA -1.1 -2.1 3.1 0 1 2 -36.6 56.4 -1.6 6 II 42.1 48.4 49.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0475 XM_371822 Huesken C6orf110 55362 GACGACAUUGAUGACCAGGca CCUGGUCAUCAAUGUCGUC -3.3 -2.4 1.9 0 1 2 -38.8 54.3 8 3 II 52.6 50.1 60.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0476 XM_371822 Huesken C6orf110 55362 UGAUGACCAGGCAGCGCAGcc CUGCGCUGCCUGGUCAUCA -2.1 -2.1 0.4 -1 3 4 -44.1 40.9 -4.9 4 Ib 63.2 49.4 66.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0477 XM_371822 Huesken C6orf110 55362 GCAGCGCAGCCACCAGAUGaa CAUCUGGUGGCUGCGCUGC -2.1 -3.4 -2.2 1 0 4 -45.1 24.6 0.1 -1 II 68.4 31.4 29.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0478 XM_371822 Huesken C6orf110 55362 CACCAGAUGAAGCCUCGGAug UCCGAGGCUUCAUCUGGUG -2.4 -2.1 -0.6 1 -2 3 -42.1 45.6 1.7 3 III 57.9 38.5 29.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0479 XM_371822 Huesken C6orf110 55362 UGUGCAGGGACUCGCUGCAgg UGCAGCGAGUCCCUGCACA -2.1 -2.1 -4.5 0 1 3 -45.2 44.5 -0.7 4 II 63.2 46.7 25.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0480 XM_371822 Huesken C6orf110 55362 CAGCCCUGGCAUUUACACAcg UGUGUAAAUGCCAGGGCUG -2.1 -2.1 -1.9 2 -2 4 -40 62.2 1.9 1 III 52.6 42 66.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0481 XM_371822 Huesken C6orf110 55362 GCCCUGGCAUUUACACACGuu CGUGUGUAAAUGCCAGGGC -2.4 -3.4 -0.7 1 0 4 -40.4 42.2 0.4 1 II 57.9 41.3 52.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0482 XM_371822 Huesken C6orf110 55362 UGUGGAAGGUGACAAAGGCca GCCUUUGUCACCUUCCACA -3.4 -2.1 1.5 1 4 3 -40 49.2 9.8 5 Ib 52.6 60.1 72.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0483 XM_371822 Huesken C6orf110 55362 CCAAGAGGCUUCUCAUUCAcc UGAAUGAGAAGCCUCUUGG -2.1 -3.3 -1.6 0 -3 3 -38.1 48.8 -8.1 3 III 47.4 37.6 39.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0484 XM_371822 Huesken C6orf110 55362 CAAGAGGCUUCUCAUUCACcu GUGAAUGAGAAGCCUCUUG -2.2 -2.1 -1.6 -1 1 3 -37 55.4 11.2 3 II 47.4 49.2 69.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0485 XM_371822 Huesken C6orf110 55362 UCCUUCUCCCGCUUGUAGUcu ACUACAAGCGGGAGAAGGA -2.2 -2.4 1.2 2 1 5 -40.9 78.5 -4 6 II 52.6 56.2 72 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0486 XM_371822 Huesken C6orf110 55362 CUCCAGCUUUGUGUAGUACuc GUACUACACAAAGCUGGAG -2.2 -2.1 0.7 0 0 2 -37 60.2 13.5 3 II 47.4 41.2 58.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0487 XM_371822 Huesken C6orf110 55362 GGGGUUGAUCAUGGUAGGCac GCCUACCAUGAUCAACCCC -3.4 -3.3 4.7 -1 1 4 -41.9 44.8 12.7 1 II 57.9 39.8 39.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0488 XM_371822 Huesken C6orf110 55362 UGGUAGGCACGUUCUCCUUgc AAGGAGAACGUGCCUACCA -0.9 -2.1 -1.6 0 0 3 -40.7 63 1.8 5 II 52.6 52.2 70.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0489 XM_371822 Huesken C6orf110 55362 GGGUAGGCUUCCUCAAAAUgc AUUUUGAGGAAGCCUACCC -1.1 -3.3 -0.3 0 -3 3 -38 50.2 -6 3 III 47.4 29.7 27.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0490 XM_371822 Huesken C6orf110 55362 GUAGGCUUCCUCAAAAUGCuu GCAUUUUGAGGAAGCCUAC -3.4 -2.2 -0.3 2 2 3 -36.9 59.6 2.5 4 II 47.4 59.9 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0491 XM_371822 Huesken C6orf110 55362 GAUUCCAUUGAUGAAGAGGgu CCUCUUCAUCAAUGGAAUC -3.3 -2.4 -0.1 0 2 2 -35.1 72.9 5.3 4 II 42.1 52.1 73.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0492 XM_371822 Huesken C6orf110 55362 CCGCUUCACCAGAUCAUCCuc GGAUGAUCUGGUGAAGCGG -3.3 -3.3 0.4 1 0 4 -41.1 55.9 7.4 1 II 57.9 50.6 63.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0493 XM_371822 Huesken C6orf110 55362 UUCACCAGAUCAUCCUCCUug AGGAGGAUGAUCUGGUGAA -2.1 -0.9 -0.7 0 2 2 -39.8 72.7 -6.3 6 II 47.4 64.2 77.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0494 XM_371822 Huesken C6orf110 55362 GAGCAGCAGAUACAGGAAGgc CUUCCUGUAUCUGCUGCUC -2.1 -2.4 0.6 2 0 2 -39.6 40.5 5.1 3 II 52.6 41.2 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0495 XM_371822 Huesken C6orf110 55362 UUGUUCCCUGAUUUCAAGUug ACUUGAAAUCAGGGAACAA -2.2 -0.9 -3.1 0 2 3 -34.3 92.6 3.7 5 II 36.8 67.2 34.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0496 XM_371822 Huesken C6orf110 55362 CAAGUUGGCAAUGGUGGUUcu AACCACCAUUGCCAACUUG -0.9 -2.1 2.6 -1 -1 3 -37.2 55.7 -0.7 5 II 47.4 44.3 34.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0497 XM_371822 Huesken C6orf110 55362 GGCAAUGGUGGUUCUCCCAaa UGGGAGAACCACCAUUGCC -2.1 -3.3 -2.3 0 -2 3 -42.5 51 2 1 III 57.9 34.2 43.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0498 XM_371822 Huesken C6orf110 55362 GAGAAGUUGACAGGCAGCAcg UGCUGCCUGUCAACUUCUC -2.1 -2.4 1.3 1 -1 3 -40.3 42.7 -3.4 5 II 52.6 41.6 60.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0499 XM_371822 Huesken C6orf110 55362 AGAGGACGCCCACAACCACca GUGGUUGUGGGCGUCCUCU -2.2 -2.1 -0.1 2 3 5 -44 29.9 7.5 2 II 63.2 44.8 53.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0500 XM_371822 Huesken C6orf110 55362 GAUGUGCCGCUGAAAGGACag GUCCUUUCAGCGGCACAUC -2.2 -2.4 -1 1 2 5 -40.8 39.7 4.8 1 II 57.9 41.1 65.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0501 XM_371822 Huesken C6orf110 55362 ACCAUUGUCCCUUUGGUCAaa UGACCAAAGGGACAAUGGU -2.1 -2.2 -1.4 2 0 3 -38.9 75.9 -0.8 5 II 47.4 51 70.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0502 XM_371822 Huesken C6orf110 55362 GUCAAAGUCAACGGAGCUGga CAGCUCCGUUGACUUUGAC -2.1 -2.2 -0.6 0 1 3 -38.2 47.4 2.7 5 II 52.6 44.1 84.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0503 NM_015213 Huesken RAB6IP1 23258 CAGCACACGAAUCAAGGAAuu UUCCUUGAUUCGUGUGCUG -0.9 -2.1 2.8 1 -3 2 -37.1 52.6 4.7 4 III 47.4 36.4 22.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0504 NM_015213 Huesken RAB6IP1 23258 AGCCAGCAGGGCAAUCCAGug CUGGAUUGCCCUGCUGGCU -2.1 -2.1 -3.1 3 2 4 -44.6 33 -2.2 1 II 63.2 42.6 63.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0505 NM_015213 Huesken RAB6IP1 23258 UAAUGUCUCAUAAUAGGUUug AACCUAUUAUGAGACAUUA -0.9 -1.3 1.3 1 3 2 -30.8 84.3 -4.2 7 II 26.3 69.6 66.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0506 NM_015213 Huesken RAB6IP1 23258 CUCCACAGAGCAACAGCGUca ACGCUGUUGCUCUGUGGAG -2.2 -2.1 -1.3 0 -1 3 -41.6 37.2 -8.2 1 III 57.9 41.1 60.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0507 NM_015213 Huesken RAB6IP1 23258 CUCAGGCUUAUGGAAGUGCuu GCACUUCCAUAAGCCUGAG -3.4 -2.1 0.8 -1 0 3 -39.3 51.1 5.4 4 II 52.6 52.4 78.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0508 NM_015213 Huesken RAB6IP1 23258 GCUGGGAUGUGAGCAGCUCcc GAGCUGCUCACAUCCCAGC -2.4 -3.4 -2.1 1 1 3 -44.1 31.2 7.4 0 II 63.2 37.1 42.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0509 NM_015213 Huesken RAB6IP1 23258 CACAUACUCCACCAGCCAUuu AUGGCUGGUGGAGUAUGUG -1.1 -2.1 -0.3 0 -2 3 -40.5 55 -3.6 3 II 52.6 36.2 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0510 NM_015213 Huesken RAB6IP1 23258 GUAAGCUUCCCCAAGUUCUgg AGAACUUGGGGAAGCUUAC -2.1 -2.2 -1.1 2 0 4 -37.9 64.3 -11.3 4 II 47.4 52.7 88.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0511 NM_015213 Huesken RAB6IP1 23258 CUUCCCCAAGUUCUGGCACuc GUGCCAGAACUUGGGGAAG -2.2 -2.1 -1.3 0 2 4 -41.1 58.7 13.2 0 II 57.9 44.5 41.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0512 NM_015213 Huesken RAB6IP1 23258 UGUCUCACCCAAUUCUCCUga AGGAGAAUUGGGUGAGACA -2.1 -2.1 1.7 2 3 3 -39.4 76.9 0.7 6 II 47.4 64.6 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0513 NM_015213 Huesken RAB6IP1 23258 UCUUGCUUGGUACGAUCAGaa CUGAUCGUACCAAGCAAGA -2.1 -2.4 0.6 1 3 2 -37.5 61.7 2.4 6 Ib 47.4 56.3 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0514 NM_015213 Huesken RAB6IP1 23258 UAAUCGACGGCAUUGAAAGac CUUUCAAUGCCGUCGAUUA -2.1 -1.3 2.2 1 4 4 -34.3 78.1 0 7 Ia 42.1 70.9 76.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0515 NM_015213 Huesken RAB6IP1 23258 CGACGGCAUUGAAAGACAGga CUGUCUUUCAAUGCCGUCG -2.1 -2.4 1.6 0 0 4 -37.4 36 -4.6 1 II 52.6 38.3 47.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0516 NM_015213 Huesken RAB6IP1 23258 UCCCCGAUGUUCUGGAUGUgc ACAUCCAGAACAUCGGGGA -2.2 -2.4 -1.3 1 0 5 -41.1 55.6 -6.3 4 II 52.6 50.9 44.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0517 NM_015213 Huesken RAB6IP1 23258 GAAUCAGGGAGAUCCUCAGgg CUGAGGAUCUCCCUGAUUC -2.1 -2.4 -2.9 1 2 3 -40 57.7 0 4 II 52.6 45.1 60.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0518 NM_015213 Huesken RAB6IP1 23258 GGGACCAUAAGGCUGAUUUcc AAAUCAGCCUUAUGGUCCC -0.9 -3.3 -2.1 0 -2 3 -38.2 69.5 0.8 3 III 47.4 39.2 41.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0519 NM_015213 Huesken RAB6IP1 23258 ACCAUAAGGCUGAUUUCCCcu GGGAAAUCAGCCUUAUGGU -3.3 -2.2 -2 2 4 3 -38.2 62.1 7.1 4 Ia 47.4 60.5 61.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0520 NM_015213 Huesken RAB6IP1 23258 UUAUUGCGGCAUUCCUUCAgc UGAAGGAAUGCCGCAAUAA -2.1 -0.9 -0.9 1 1 5 -36.1 80.7 1.6 8 II 42.1 63.2 77.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0521 NM_015213 Huesken RAB6IP1 23258 ACAGUUUGGGCUGGCGGAUag AUCCGCCAGCCCAAACUGU -1.1 -2.2 -0.8 2 1 5 -42.6 41.4 -3.3 4 II 57.9 41.3 40.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0522 NM_015213 Huesken RAB6IP1 23258 UGGAUGUACUUCUCCCUCUgg AGAGGGAGAAGUACAUCCA -2.1 -2.1 -2.9 2 0 3 -39.8 72.6 -6.3 6 II 47.4 66.3 80.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0523 NM_015213 Huesken RAB6IP1 23258 CACUUGUUGCUGGCUGGCCca GGCCAGCCAGCAACAAGUG -3.3 -2.1 -1.8 1 1 4 -43.1 52.7 5.4 2 II 63.2 52 73.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0524 NM_015213 Huesken RAB6IP1 23258 CCUUGUCCAAUCUUCAUGUca ACAUGAAGAUUGGACAAGG -2.2 -3.3 0.9 -1 -1 2 -35.7 73 -6 4 III 42.1 45.9 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0525 NM_015213 Huesken RAB6IP1 23258 GAAUUGCAGUAUGGUCAAUuu AUUGACCAUACUGCAAUUC -1.1 -2.4 1.4 0 -1 2 -33.7 59.1 1.4 4 II 36.8 31.3 45.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0526 NM_015213 Huesken RAB6IP1 23258 GAUGUACGGAGAGUAGGUGuc CACCUACUCUCCGUACAUC -2.1 -2.4 0.6 1 3 3 -39.2 48 2.3 4 II 52.6 41.6 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0527 NM_015213 Huesken RAB6IP1 23258 GUAGGUGUCCGAACAUUCAac UGAAUGUUCGGACACCUAC -2.1 -2.2 0.5 1 -1 3 -37.6 53.1 -6.3 4 III 47.4 45 49 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0528 NM_015213 Huesken RAB6IP1 23258 UUAUUUUGUUGUCAAUGAAag UUCAUUGACAACAAAAUAA -0.9 -0.9 0.9 1 1 1 -27.4 95.3 1.7 8 II 21.1 62 97.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0529 NM_015213 Huesken RAB6IP1 23258 UGAAAGAUGCAAACAUCUGgg CAGAUGUUUGCAUCUUUCA -2.1 -2.1 -4.2 1 3 2 -33.3 68.1 2.4 6 Ia 36.8 69.2 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0530 NM_015213 Huesken RAB6IP1 23258 AGAUGCAAACAUCUGGGUCuc GACCCAGAUGUUUGCAUCU -2.4 -2.1 -4.1 1 4 3 -38.2 70 17.5 4 Ib 47.4 56.6 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0531 NM_015213 Huesken RAB6IP1 23258 CUUGAGAGGAAGGGCAGGUag ACCUGCCCUUCCUCUCAAG -2.2 -2.1 2 -1 0 4 -42.5 37.5 -1 4 II 57.9 43.7 53.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0532 NM_015213 Huesken RAB6IP1 23258 GUUUUGCAUUUGCUCCCUGuu CAGGGAGCAAAUGCAAAAC -2.1 -2.2 -1.5 0 3 3 -36.2 63.9 4.7 3 II 47.4 48.7 67.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0533 NM_015213 Huesken RAB6IP1 23258 UUUGCAUUUGCUCCCUGUUgg AACAGGGAGCAAAUGCAAA -0.9 -0.9 -1.5 1 2 3 -36.2 79.3 -0.9 5 II 42.1 63.5 49.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0534 NM_015213 Huesken RAB6IP1 23258 UAUCCUGGCUGGGUUGGAUga AUCCAACCCAGCCAGGAUA -1.1 -1.3 -2 2 3 3 -41.8 63.3 -1.6 5 II 52.6 51.5 51.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0535 NM_015213 Huesken RAB6IP1 23258 GUAAAUCCUGAGUUCUUCUuc AGAAGAACUCAGGAUUUAC -2.1 -2.2 0.8 0 1 2 -33.8 79.8 3.4 5 II 36.8 53.1 44.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0536 NM_015213 Huesken RAB6IP1 23258 UUUCCAGGCUCACCCCAGUuc ACUGGGGUGAGCCUGGAAA -2.2 -0.9 -4.6 2 2 4 -43.5 52.6 -3.9 4 II 57.9 57 37.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0537 NM_015213 Huesken RAB6IP1 23258 UUCCAGGCUCACCCCAGUUcu AACUGGGGUGAGCCUGGAA -0.9 -0.9 -4.6 1 1 4 -43.5 52.2 1.1 4 II 57.9 57.4 58.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0538 NM_015213 Huesken RAB6IP1 23258 CAAGGCUUGCAGCCGGGCAau UGCCCGGCUGCAAGCCUUG -2.1 -2.1 -4.3 1 -1 7 -45.7 40 -1.1 1 III 68.4 39.8 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0539 NM_015213 Huesken RAB6IP1 23258 CGUAGGAAUGCAAAGGGGAgc UCCCCUUUGCAUUCCUACG -2.4 -2.4 2.8 -1 -2 4 -39.5 37.1 -10.7 3 III 52.6 37.7 44.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0540 NM_015213 Huesken RAB6IP1 23258 GGCCCGCAGCCUCUUCAGCuu GCUGAAGAGGCUGCGGGCC -3.4 -3.3 -3.1 2 1 7 -47.5 36.6 12.8 -2 II 73.7 31.4 37.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0541 NM_015213 Huesken RAB6IP1 23258 UUCAGCUUGGAGGCACUCUca AGAGUGCCUCCAAGCUGAA -2.1 -0.9 -0.4 2 1 3 -41.4 65.5 -1.7 7 II 52.6 64.2 66.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0542 NM_015213 Huesken RAB6IP1 23258 GUUGGGGAACUGUGGCAAGuc CUUGCCACAGUUCCCCAAC -2.1 -2.2 2.2 -1 1 4 -40.9 38.7 0 2 II 57.9 38.8 50.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0543 NM_015213 Huesken RAB6IP1 23258 GGCAAGUCCUCUGGCAACUca AGUUGCCAGAGGACUUGCC -2.1 -3.3 0.4 1 -2 3 -42.4 43.3 -0.6 2 III 57.9 34.6 71.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0544 NM_015213 Huesken RAB6IP1 23258 CACAAAGCAGAGGUUAGCCuc GGCUAACCUCUGCUUUGUG -3.3 -2.1 -1.5 -1 2 3 -38.9 56.3 12.7 3 II 52.6 52.3 70.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0545 NM_015213 Huesken RAB6IP1 23258 CAGAGGUUAGCCUCUUGAGgc CUCAAGAGGCUAACCUCUG -2.1 -2.1 -5.9 0 0 3 -39.3 60.6 -6.7 2 II 52.6 47.4 52.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0546 NM_015213 Huesken RAB6IP1 23258 AGUCAUCAGUCUCUGGUAAug UUACCAGAGACUGAUGACU -0.9 -2.1 0.1 3 0 2 -37.5 64.2 4.4 5 II 42.1 36.2 28.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0547 NM_015213 Huesken RAB6IP1 23258 UGGCCCAUAGACCCCAGAAaa UUCUGGGGUCUAUGGGCCA -0.9 -2.1 -5.2 1 -1 5 -44 54.6 -1.4 2 II 57.9 45.7 63.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0548 NM_015213 Huesken RAB6IP1 23258 AGGAGGUGGGAGCGGCACCuc GGUGCCGCUCCCACCUCCU -3.3 -2.1 -3.6 2 2 5 -48.7 34.5 12.1 2 II 73.7 52.4 39 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0549 NM_015213 Huesken RAB6IP1 23258 UGCCUGGUGGAGUUGCUCCag GGAGCAACUCCACCAGGCA -3.3 -2.1 -3.8 2 3 3 -44.8 62.7 12 4 II 63.2 65.4 62.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0550 NM_015213 Huesken RAB6IP1 23258 UCCAGCACGCUCCGACAUGcc CAUGUCGGAGCGUGCUGGA -2.1 -2.4 -2.4 0 1 3 -43.5 41.6 0.1 3 II 63.2 53.3 60.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0551 NM_015213 Huesken RAB6IP1 23258 UGCACUUAGAGACGUAGAGag CUCUACGUCUCUAAGUGCA -2.1 -2.1 0.1 1 2 2 -37.8 69.1 2.4 6 Ib 47.4 57.9 68.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0552 NM_015213 Huesken RAB6IP1 23258 UGUGAGGGCAAACCCAAAUgu AUUUGGGUUUGCCCUCACA -1.1 -2.1 -4.4 1 0 4 -38.6 58.9 3.4 6 II 47.4 56.3 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0553 NM_015213 Huesken RAB6IP1 23258 UGUGAUAAUAAAGGCAUGGaa CCAUGCCUUUAUUAUCACA -3.3 -2.1 3.4 -1 3 3 -33.7 71 5 8 Ia 36.8 71 72.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0554 NM_015213 Huesken RAB6IP1 23258 AAGGCAUGGAAUUGGGGCUcc AGCCCCAAUUCCAUGCCUU -2.1 -0.9 1.4 2 2 5 -41.1 60.4 1.4 5 II 52.6 53.3 57.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0555 NM_015213 Huesken RAB6IP1 23258 CUGGGAUCAGCCUGGGUCUug AGACCCAGGCUGAUCCCAG -2.1 -2.1 -0.5 -1 -2 3 -45.1 41.6 -10.7 2 III 63.2 41.8 75.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0556 NM_015213 Huesken RAB6IP1 23258 CCUACUGCAUCUUGGUCAAag UUGACCAAGAUGCAGUAGG -0.9 -3.3 1.3 -2 -3 2 -38.1 58.4 -5.1 3 III 47.4 26.4 57.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0557 NM_015213 Huesken RAB6IP1 23258 AAAAUUUUCUCCUUCAGUCgu GACUGAAGGAGAAAAUUUU -2.4 -0.9 1.2 3 5 2 -30.9 96.7 5 7 Ia 31.6 75.7 90.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0558 NM_015213 Huesken RAB6IP1 23258 AAGGGCUGGCACCAUCCCUgg AGGGAUGGUGCCAGCCCUU -2.1 -0.9 -3.1 3 2 4 -45.8 45.6 -1.6 2 II 63.2 54.1 83.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0559 NM_015213 Huesken RAB6IP1 23258 CCAUCCCUGGCUUUAGAAGcc CUUCUAAAGCCAGGGAUGG -2.1 -3.3 -1.1 0 0 3 -39.1 62.2 1 1 II 52.6 37.6 46.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0560 NM_015213 Huesken RAB6IP1 23258 ACUGGCAUAAUGCCGACAGcu CUGUCGGCAUUAUGCCAGU -2.1 -2.2 -4.9 1 3 4 -39.6 57.1 2.4 4 II 52.6 54.7 73 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0561 NM_015213 Huesken RAB6IP1 23258 GUGAUGUUGAACUCCUGCAau UGCAGGAGUUCAACAUCAC -2.1 -2.2 0.4 2 -1 2 -38.1 69.9 -3.8 5 II 47.4 49.8 62.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0562 NM_015213 Huesken RAB6IP1 23258 AAUGUCUGCAGCACACGAAuc UUCGUGUGCUGCAGACAUU -0.9 -0.9 -0.4 3 1 2 -38.2 62.8 -8.7 7 II 47.4 50.7 40.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0563 NM_015213 Huesken RAB6IP1 23258 GAGGUGAUCUCUGGCUCCCaa GGGAGCCAGAGAUCACCUC -3.3 -2.4 -0.6 0 2 3 -44.5 44.8 8.1 2 II 63.2 48.8 49.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0564 NM_015213 Huesken RAB6IP1 23258 AUCGGCAGAAGUUCCGGGCuc GCCCGGAACUUCUGCCGAU -3.4 -1.1 -2.8 1 4 6 -43.4 58.1 10.4 3 II 63.2 61 70.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0565 NM_015213 Huesken RAB6IP1 23258 AGUGCUUCACAAUGCCAUUga AAUGGCAUUGUGAAGCACU -0.9 -2.1 -1 1 0 3 -36.5 67.5 -1.7 3 II 42.1 49.1 60.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0566 NM_015213 Huesken RAB6IP1 23258 GACUGCUGCAGCGGCGGGGuc CCCCGCCGCUGCAGCAGUC -3.3 -2.4 -1.5 1 2 9 -48.8 33.1 -2.4 2 II 78.9 39.2 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0567 NM_015213 Huesken RAB6IP1 23258 UCCGGCAUGGCCUCUCAUCca GAUGAGAGGCCAUGCCGGA -2.4 -2.4 -2.9 1 1 5 -44.7 52.3 2.7 2 II 63.2 58.7 63 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0568 NM_015213 Huesken RAB6IP1 23258 AUGGCCUCUCAUCCACCUCag GAGGUGGAUGAGAGGCCAU -2.4 -1.1 -2.4 2 3 4 -43.2 64 15.1 2 II 57.9 61.5 74.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0569 NM_015213 Huesken RAB6IP1 23258 CAGCUCCCCAACUAGGAUCcg GAUCCUAGUUGGGGAGCUG -2.4 -2.1 -3.4 1 -1 4 -41.9 59.4 5.4 1 II 57.9 50.9 66.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0570 NM_015213 Huesken RAB6IP1 23258 GCUUCCAUCAUCCAUGCCCuu GGGCAUGGAUGAUGGAAGC -3.3 -3.4 0.2 1 2 4 -41.9 62.1 7.5 3 II 57.9 52.6 54.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0571 NM_015213 Huesken RAB6IP1 23258 UCCACCAGCCAUUUGGCAUac AUGCCAAAUGGCUGGUGGA -1.1 -2.4 -4.1 1 1 3 -41.2 72.3 3.7 4 II 52.6 50.9 69.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0572 NM_015213 Huesken RAB6IP1 23258 AUCCAUGGGUUGGCAGUGAac UCACUGCCAACCCAUGGAU -2.4 -1.1 -1.4 3 0 3 -41.5 43.3 -1.1 5 II 52.6 44.4 57.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0573 NM_015213 Huesken RAB6IP1 23258 AAUCGACGGCAUUGAAAGAca UCUUUCAAUGCCGUCGAUU -2.4 -0.9 2.2 2 1 4 -35.4 55.3 1.6 4 II 42.1 40.9 52.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0574 NM_015213 Huesken RAB6IP1 23258 GAAAGACAGGAGGUGAUAGag CUAUCACCUCCUGUCUUUC -2.1 -2.4 2.6 1 2 2 -37.4 53.9 4.6 4 II 47.4 42.2 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0575 NM_015213 Huesken RAB6IP1 23258 GGAUGUGCCUCAUAUCCUGaa CAGGAUAUGAGGCACAUCC -2.1 -3.3 -0.9 1 1 3 -39.9 52.1 -2.4 3 II 52.6 44.2 46.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0576 NM_015213 Huesken RAB6IP1 23258 GGAGGCAUGAGUGAGCUGGca CCAGCUCACUCAUGCCUCC -3.3 -3.3 -0.8 1 1 3 -44 44 3 3 II 63.2 45.3 64.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0577 NM_015213 Huesken RAB6IP1 23258 CCUACGUUCUGAAUCAAGAag UCUUGAUUCAGAACGUAGG -2.4 -3.3 0.5 1 -2 2 -35.3 66 -6 3 III 42.1 42.4 29.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0578 NM_015213 Huesken RAB6IP1 23258 UUUCUCUGCCGGUUGUCCUga AGGACAACCGGCAGAGAAA -2.1 -0.9 -0.7 3 4 5 -40.5 79.2 -1.6 7 II 52.6 67.4 67 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0579 NM_015213 Huesken RAB6IP1 23258 AACAGGUGGGACCAUAAGGcu CCUUAUGGUCCCACCUGUU -3.3 -0.9 -0.8 3 3 3 -40.2 58.9 2.4 5 Ib 52.6 62.3 62.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0580 NM_015213 Huesken RAB6IP1 23258 GAUCCUUUCCAGGAGAUCAca UGAUCUCCUGGAAAGGAUC -2.1 -2.4 -5.3 3 -1 2 -38.8 66.5 -1.5 3 II 47.4 45.6 44.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0581 NM_015213 Huesken RAB6IP1 23258 UUUCCAGGAGAUCACAAAGgc CUUUGUGAUCUCCUGGAAA -2.1 -0.9 0.8 1 3 2 -35.7 73.5 7.7 6 Ib 42.1 65.6 65.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0582 NM_015213 Huesken RAB6IP1 23258 AGGAGAUCACAAAGGCUGGca CCAGCCUUUGUGAUCUCCU -3.3 -2.1 1.8 1 2 3 -40.3 50.6 -0.3 5 Ib 52.6 52.8 47.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0583 NM_015213 Huesken RAB6IP1 23258 GAUCACAAAGGCUGGCAAUca AUUGCCAGCCUUUGUGAUC -1.1 -2.4 0.6 0 -1 3 -37.9 53 -3.6 4 II 47.4 33.7 48.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0584 NM_015213 Huesken RAB6IP1 23258 UCUUGGUCUUAUUGCGGCAuu UGCCGCAAUAAGACCAAGA -2.1 -2.4 3.3 0 1 5 -38.4 67.6 1.6 6 II 47.4 53 69.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0585 NM_015213 Huesken RAB6IP1 23258 GAUGUACUUCUCCCUCUGGuc CCAGAGGGAGAAGUACAUC -3.3 -2.4 -0.2 0 2 3 -39.8 58.7 0.1 4 II 52.6 46.6 34.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0586 NM_015213 Huesken RAB6IP1 23258 CUCUGGUCAUUAUCUAAACgc GUUUAGAUAAUGACCAGAG -2.2 -2.1 0.5 0 -1 2 -32.9 73.4 5.4 3 II 36.8 51.6 51.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0587 NM_015213 Huesken RAB6IP1 23258 CAGUGGAAAGUACAUCAGAcu UCUGAUGUACUUUCCACUG -2.4 -2.1 1.6 -1 -3 2 -36 50.4 -3.4 3 III 42.1 43.5 47.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0588 NM_015213 Huesken RAB6IP1 23258 AUUCAACAGCCUGAUCUUGuc CAAGAUCAGGCUGUUGAAU -2.1 -1.1 -0.4 3 3 3 -35.7 60 3.4 6 Ia 42.1 55 55.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0589 NM_015213 Huesken RAB6IP1 23258 GGUCUCCAGGAAUCUUGAGag CUCAAGAUUCCUGGAGACC -2.1 -3.3 -0.5 2 1 2 -39.6 54.2 2.3 2 II 52.6 32.6 64.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0590 NM_015213 Huesken RAB6IP1 23258 GCUUUAUCAAAGUUUUGCAuu UGCAAAACUUUGAUAAAGC -2.1 -3.4 1 1 0 2 -30.6 85.3 0.9 5 II 31.6 41.8 46 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0591 NM_015213 Huesken RAB6IP1 23258 GGAUGACAAACGCCUCAUAau UAUGAGGCGUUUGUCAUCC -1.3 -3.3 -1.4 0 -3 4 -37.7 47.1 -3.7 2 III 47.4 26.7 44.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0592 NM_015213 Huesken RAB6IP1 23258 GCCUCAUAAUCUGCAAACAuc UGUUUGCAGAUUAUGAGGC -2.1 -3.4 1 1 -3 3 -35.9 57.4 -3.1 2 III 42.1 29.7 38.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0593 NM_015213 Huesken RAB6IP1 23258 UGCAAACAUCUGAGUGAAAcg UUUCACUCAGAUGUUUGCA -0.9 -2.1 1.3 -1 -2 2 -34.4 53.5 -3.6 5 II 36.8 39.5 42.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0594 NM_015213 Huesken RAB6IP1 23258 AACUUCCCGGAUCUGAAUGuu CAUUCAGAUCCGGGAAGUU -2.1 -0.9 0.3 2 3 5 -37.4 77.7 10.1 5 Ib 47.4 57.2 74.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0595 NM_015213 Huesken RAB6IP1 23258 UUCUUCUUCAUCACACUGAac UCAGUGUGAUGAAGAAGAA -2.4 -0.9 -0.5 2 0 1 -34.9 86.1 -8.7 9 II 36.8 68.8 75.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0596 NM_015213 Huesken RAB6IP1 23258 ACUUUGAGAUCCUUAUUGCug GCAAUAAGGAUCUCAAAGU -3.4 -2.2 2.5 1 4 2 -33.7 81.5 5 7 Ia 36.8 60.5 66.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0597 NM_015213 Huesken RAB6IP1 23258 UCCUUAUUGCUGCUGGGGUcu ACCCCAGCAGCAAUAAGGA -2.2 -2.4 0.4 2 2 4 -41.4 65.5 0.8 6 II 52.6 53.3 64.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0598 NM_015213 Huesken RAB6IP1 23258 ACGCACUUCCAACUUUUCCag GGAAAAGUUGGAAGUGCGU -3.3 -2.2 0.7 4 3 3 -36.7 73.5 17.1 5 II 47.4 61.6 60.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0599 NM_015213 Huesken RAB6IP1 23258 CUUAAGAAGCUCGUAGGAAug UUCCUACGAGCUUCUUAAG -0.9 -2.1 1.7 0 -1 2 -35.2 51 -3.1 5 II 42.1 39.2 59.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0600 NM_015213 Huesken RAB6IP1 23258 UUAAGAAGCUCGUAGGAAUgc AUUCCUACGAGCUUCUUAA -1.1 -0.9 1.4 1 1 2 -34.2 69.5 -6.3 7 II 36.8 60.9 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0601 NM_015213 Huesken RAB6IP1 23258 GAAGCUCGUAGGAAUGCAAag UUGCAUUCCUACGAGCUUC -0.9 -2.4 0.4 0 -1 2 -37.5 51.2 -6.3 3 III 47.4 35.1 50.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0602 NM_015213 Huesken RAB6IP1 23258 AGCCAGCAAUGUUCCCAUUcc AAUGGGAACAUUGCUGGCU -0.9 -2.1 -2.6 2 -1 3 -38.8 55.8 1.8 2 II 47.4 39.1 43.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0603 NM_015213 Huesken RAB6IP1 23258 GCCAGCAAUGUUCCCAUUCcu GAAUGGGAACAUUGCUGGC -2.4 -3.4 -3 0 -1 3 -39.1 56.4 12.8 2 II 52.6 45.6 45.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0604 NM_015213 Huesken RAB6IP1 23258 GCAAUGUUCCCAUUCCUCUug AGAGGAAUGGGAACAUUGC -2.1 -3.4 -3 2 0 3 -38.1 67.2 -4 4 II 47.4 49.2 53.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0605 NM_015213 Huesken RAB6IP1 23258 CAAUGUUCCCAUUCCUCUUgu AAGAGGAAUGGGAACAUUG -0.9 -2.1 -3 1 -1 3 -35.6 79 -0.7 3 II 42.1 52.1 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0606 NM_015213 Huesken RAB6IP1 23258 GCCCGCAGCCUCUUCAGCUug AGCUGAAGAGGCUGCGGGC -2.1 -3.4 -3 2 0 6 -46.3 37.3 -4 -1 III 68.4 35.3 54.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0607 NM_015213 Huesken RAB6IP1 23258 CCAAUUUGUUGGGGAACUGug CAGUUCCCCAACAAAUUGG -2.1 -3.3 -1.1 -1 0 4 -36.1 52.9 -2 3 II 47.4 45.1 67.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0608 NM_015213 Huesken RAB6IP1 23258 CAAUGAAGUGGUUGUCAAUgu AUUGACAACCACUUCAUUG -1.1 -2.1 0.6 -2 -2 2 -33.1 64.1 -3 4 II 36.8 39.3 48.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0609 NM_015213 Huesken RAB6IP1 23258 AGCUUUGACCGGUCAUCCAgg UGGAUGACCGGUCAAAGCU -2.1 -2.1 -1 2 0 4 -40.7 61.6 -3.8 4 II 52.6 45.5 67.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0610 NM_015213 Huesken RAB6IP1 23258 AUCUAAGAAAUGCAGGAGAga UCUCCUGCAUUUCUUAGAU -2.4 -1.1 1.2 1 0 2 -35.1 63.1 1.4 7 II 36.8 51.9 51.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0611 NM_015213 Huesken RAB6IP1 23258 UUUGACAGGAAAGUCAAAUag AUUUGACUUUCCUGUCAAA -1.1 -0.9 -4.9 1 2 2 -31.9 77.3 3.4 7 II 31.6 66.6 53.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0612 NM_015213 Huesken RAB6IP1 23258 UAUUGGCCCAUAGACCCCAga UGGGGUCUAUGGGCCAAUA -2.1 -1.3 -5.2 1 2 5 -41.9 54.1 -3.8 6 II 52.6 63.2 66.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0613 NM_015213 Huesken RAB6IP1 23258 CCAGGAGGUGGGAGCGGCAcc UGCCGCUCCCACCUCCUGG -2.1 -3.3 -0.3 -2 -2 5 -48.6 10.4 -8.3 1 III 73.7 27.2 24.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0614 NM_015213 Huesken RAB6IP1 23258 UGUAUAUGUAGCUCUCAAGgg CUUGAGAGCUACAUAUACA -2.1 -2.1 2.4 1 2 2 -34.3 87.4 -2.4 8 Ia 36.8 66.6 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0615 NM_015213 Huesken RAB6IP1 23258 CAUAGGAGUUGAAGCGCUGca CAGCGCUUCAACUCCUAUG -2.1 -2.1 2.5 -2 1 4 -38.4 44.6 -4.6 4 II 52.6 48.3 49.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0616 NM_015213 Huesken RAB6IP1 23258 UGCAGUUUGGUCACAGGAGug CUCCUGUGACCAAACUGCA -2.1 -2.1 0.6 2 2 2 -40 59.6 -4.9 5 Ib 52.6 60.5 80.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0617 NM_015213 Huesken RAB6IP1 23258 CAGGAGUGUCUUCACCAUCcu GAUGGUGAAGACACUCCUG -2.4 -2.1 -1.7 0 -1 2 -39.5 52.2 13.5 2 II 52.6 54.9 82.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0618 NM_015213 Huesken RAB6IP1 23258 ACUCAGCAUUGUGCAUGUGgu CACAUGCACAAUGCUGAGU -2.1 -2.2 -0.8 2 3 2 -37.8 51.6 5.7 4 II 47.4 44.6 69.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0619 NM_015213 Huesken RAB6IP1 23258 AUUGUGCAUGUGGUAGAGGgu CCUCUACCACAUGCACAAU -3.3 -1.1 3.3 1 5 2 -38.1 57.4 2.3 5 Ib 47.4 61.1 68.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0620 NM_015213 Huesken RAB6IP1 23258 GCAUUGCACUGCAGAUCUGcu CAGAUCUGCAGUGCAAUGC -2.1 -3.4 -1.2 0 1 2 -39.2 43.5 -4.9 2 II 52.6 34.9 56.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0621 NM_015213 Huesken RAB6IP1 23258 CUUGCUAGUCACCUCUUCAua UGAAGAGGUGACUAGCAAG -2.1 -2.1 -2.5 -1 -1 2 -38.2 70 -1.1 3 II 47.4 49.6 68.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0622 NM_015213 Huesken RAB6IP1 23258 AUGUGAGGGCAAACCCAAAug UUUGGGUUUGCCCUCACAU -0.9 -1.1 -4.4 2 -1 4 -38.6 47.2 -4 4 II 47.4 43.6 73.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0623 NM_015213 Huesken RAB6IP1 23258 AUGUCCGAGAGCCAUCCUCcc GAGGAUGGCUCUCGGACAU -2.4 -1.1 -2.6 2 3 3 -42.6 60.3 7.5 4 II 57.9 61.2 55.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0624 NM_015213 Huesken RAB6IP1 23258 GGCUCCCUGGGAUCAGCCUgg AGGCUGAUCCCAGGGAGCC -2.1 -3.3 -3.2 1 -1 3 -47.5 42.3 -4 -1 III 68.4 27.9 57.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0625 NM_015213 Huesken RAB6IP1 23258 UGGGUCUUGAAUGCCAGCCcu GGCUGGCAUUCAAGACCCA -3.3 -2.1 0.8 2 3 3 -42.5 68.8 12.7 5 II 57.9 71.7 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0626 NM_015213 Huesken RAB6IP1 23258 AUUUGAAUGUUCUUCUCAAug UUGAGAAGAACAUUCAAAU -0.9 -1.1 -0.7 2 2 1 -29.9 82.7 -3.8 6 II 26.3 52.9 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0627 NM_015213 Huesken RAB6IP1 23258 CAUAAUGCCGACAGCUCGUcc ACGAGCUGUCGGCAUUAUG -2.2 -2.1 -1.5 -1 0 4 -39 53.5 -5.9 4 II 52.6 47.7 54.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0628 NM_015213 Huesken RAB6IP1 23258 CGGUCUCCGUGUCCAGUCCgc GGACUGGACACGGAGACCG -3.3 -2.4 -1.9 0 -1 3 -44.8 52.6 10.8 0 II 68.4 40.2 60.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0629 NM_003347 Huesken UBE2L3 7332 AGAGUAUUCUUCAGCUAGGuc CCUAGCUGAAGAAUACUCU -3.3 -2.1 0.8 2 3 2 -36.3 61.6 -4.9 5 Ia 42.1 59.5 63.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0630 NM_003347 Huesken UBE2L3 7332 AGUAUUCUUCAGCUAGGUCag GACCUAGCUGAAGAAUACU -2.4 -2.1 1.4 1 4 2 -36.4 77.8 14.4 5 Ia 42.1 56.7 101.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0631 NM_003347 Huesken UBE2L3 7332 AUUCUUCAGCUAGGUCAGCcc GCUGACCUAGCUGAAGAAU -3.4 -1.1 -1.5 2 4 2 -38.4 54.9 7.4 4 Ia 47.4 58.1 70.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0632 NM_003347 Huesken UBE2L3 7332 CUUCAGCUAGGUCAGCCCGaa CGGGCUGACCUAGCUGAAG -2.4 -2.1 -3 0 2 5 -43 49 6.1 1 II 63.2 50.7 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0633 NM_003347 Huesken UBE2L3 7332 UCAGCUAGGUCAGCCCGAAgc UUCGGGCUGACCUAGCUGA -0.9 -2.4 -3 1 0 5 -43.3 39.4 -6.1 3 II 57.9 44.8 49 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0634 NM_003347 Huesken UBE2L3 7332 UAGGUCAGCCCGAAGCGGGug CCCGCUUCGGGCUGACCUA -3.3 -1.3 -3.7 1 4 5 -45.7 45.6 -4.9 4 Ib 68.4 66.6 62.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0635 NM_003347 Huesken UBE2L3 7332 GGUCAGCCCGAAGCGGGUGcu CACCCGCUUCGGGCUGACC -2.1 -3.3 -4.2 2 1 5 -46.6 25.4 5 0 II 73.7 31.9 60 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0636 NM_003347 Huesken UBE2L3 7332 UCAGCCCGAAGCGGGUGCUca AGCACCCGCUUCGGGCUGA -2.1 -2.4 -4.2 -1 2 5 -46.6 37.9 -6.3 3 II 68.4 46.3 37.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0637 NM_003347 Huesken UBE2L3 7332 GCCCGAAGCGGGUGCUCAGgc CUGAGCACCCGCUUCGGGC -2.1 -3.4 -4.2 1 0 5 -46.6 24.1 0 -1 II 73.7 25.7 51.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0638 NM_003347 Huesken UBE2L3 7332 CGAAGCGGGUGCUCAGGCUgg AGCCUGAGCACCCGCUUCG -2.1 -2.4 -2.5 0 -1 5 -45.4 34.1 -8.3 1 III 68.4 34.5 46.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0639 NM_003347 Huesken UBE2L3 7332 GAAGCGGGUGCUCAGGCUGgg CAGCCUGAGCACCCGCUUC -2.1 -2.4 -2.5 0 2 5 -45.1 36.2 3.1 1 II 68.4 45.1 37.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0640 NM_003347 Huesken UBE2L3 7332 GUCAUUCACCAGUGCUAUGag CAUAGCACUGGUGAAUGAC -2.1 -2.2 0.7 0 0 2 -37.2 65.6 2.3 3 II 47.4 44.1 80.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0641 NM_003347 Huesken UBE2L3 7332 UCAUUCACCAGUGCUAUGAgg UCAUAGCACUGGUGAAUGA -2.4 -2.4 -0.9 1 0 2 -37.4 79 -0.7 9 II 42.1 60.4 77.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0642 NM_003347 Huesken UBE2L3 7332 CAUUCACCAGUGCUAUGAGgg CUCAUAGCACUGGUGAAUG -2.1 -2.1 -1 -1 2 2 -37.1 63.4 2.7 2 II 47.4 40.9 77.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0643 NM_003347 Huesken UBE2L3 7332 GAGGGACUGGAUUACUUGGuc CCAAGUAAUCCAGUCCCUC -3.3 -2.4 3.6 1 1 3 -39.5 56.4 5.3 2 II 52.6 45.3 61.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0644 NM_003347 Huesken UBE2L3 7332 AGGGACUGGAUUACUUGGUcg ACCAAGUAAUCCAGUCCCU -2.2 -2.1 3.3 3 1 3 -39.3 58.7 -0.8 5 II 47.4 51.7 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0645 NM_003347 Huesken UBE2L3 7332 CUGGAUUACUUGGUCGGUUuu AACCGACCAAGUAAUCCAG -0.9 -2.1 2 1 -1 3 -37.2 54.8 -0.9 3 II 47.4 46.5 66.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0646 NM_003347 Huesken UBE2L3 7332 GAUUACUUGGUCGGUUUUGgu CAAAACCGACCAAGUAAUC -2.1 -2.4 2.2 1 1 3 -33.6 67.1 0.4 6 II 42.1 47.4 56.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0647 NM_003347 Huesken UBE2L3 7332 AUUACUUGGUCGGUUUUGGuu CCAAAACCGACCAAGUAAU -3.3 -1.1 2.2 3 5 3 -34.5 81.4 0 7 Ia 42.1 64.6 84.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0648 NM_003347 Huesken UBE2L3 7332 ACUUGGUCGGUUUUGGUUGcu CAACCAAAACCGACCAAGU -2.1 -2.2 2.9 3 3 3 -36.4 73.6 5.4 6 Ib 47.4 59.1 87 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0649 NM_003347 Huesken UBE2L3 7332 UGGUCGGUUUUGGUUGCUGgc CAGCAACCAAAACCGACCA -2.1 -2.1 0 3 3 -38.8 61.4 2.3 5 II 52.6 59 60 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0650 NM_003347 Huesken UBE2L3 7332 CGGUUUUGGUUGCUGGCUUcc AAGCCAGCAACCAAAACCG -0.9 -2.4 1 -2 3 -38.5 58.4 -1.2 3 II 52.6 38.9 41.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0651 NM_003347 Huesken UBE2L3 7332 GUUUUGGUUGCUGGCUUCCag GGAAGCCAGCAACCAAAAC -3.3 -2.2 0.4 -1 2 3 -38.5 62.8 8.1 6 II 52.6 52.9 73 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0652 NM_003347 Huesken UBE2L3 7332 UGGUUGCUGGCUUCCAGUUuu AACUGGAAGCCAGCAACCA -0.9 -2.1 -2.7 1 0 3 -40.9 65 -3.3 4 II 52.6 52.7 71.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0653 NM_003347 Huesken UBE2L3 7332 UUUCGGCACUAAUUACUGGca CCAGUAAUUAGUGCCGAAA -3.3 -0.9 0.8 2 5 4 -34.9 73.7 4.6 6 II 42.1 68.3 82.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0654 NM_003347 Huesken UBE2L3 7332 CACUAAUUACUGGCAGACAga UGUCUGCCAGUAAUUAGUG -2.1 -2.1 1.6 0 -3 3 -35.9 57.7 -3.1 4 II 42.1 40.7 51.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0655 NM_003347 Huesken UBE2L3 7332 ACUAAUUACUGGCAGACAGac CUGUCUGCCAGUAAUUAGU -2.1 -2.2 -0.2 3 3 3 -35.9 70.5 5.1 6 Ia 42.1 56.8 52.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0656 NM_003347 Huesken UBE2L3 7332 UAAUUACUGGCAGACAGACcu GUCUGUCUGCCAGUAAUUA -2.2 -1.3 -0.3 1 4 3 -36.2 65.6 5.1 7 Ia 42.1 65.8 91 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0657 NM_003347 Huesken UBE2L3 7332 AAUUACUGGCAGACAGACCug GGUCUGUCUGCCAGUAAUU -3.3 -0.9 -2.1 3 4 3 -38.2 70 9.8 6 Ia 47.4 66.4 74.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0658 NM_003347 Huesken UBE2L3 7332 UACUGGCAGACAGACCUGCcc GCAGGUCUGUCUGCCAGUA -3.4 -1.3 -4.7 1 3 3 -42.9 52 5.1 5 II 57.9 66 52.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0659 NM_003347 Huesken UBE2L3 7332 CCUGCCCCUUUUCGUCGAUgu AUCGACGAAAAGGGGCAGG -1.1 -3.3 1.3 -2 -2 5 -40.9 41.9 -0.6 0 III 57.9 22 32 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0660 NM_003347 Huesken UBE2L3 7332 UGCCCCUUUUCGUCGAUGUuu ACAUCGACGAAAAGGGGCA -2.2 -2.1 1.3 2 0 5 -39.8 70.8 -6.3 5 II 52.6 53.7 64.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0661 NM_003347 Huesken UBE2L3 7332 CCUUUUCGUCGAUGUUUGGgu CCAAACAUCGACGAAAAGG -3.3 -3.3 2 -2 0 2 -34.9 65.3 -2 4 II 47.4 40.7 59.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0662 NM_003347 Huesken UBE2L3 7332 CGUCGAUGUUUGGGUGAUAga UAUCACCCAAACAUCGACG -1.3 -2.4 2.4 0 -4 3 -36.8 37.7 -5.8 2 III 47.4 25.2 57 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0663 NM_003347 Huesken UBE2L3 7332 AUGUUUGGGUGAUAGAUCUuu AGAUCUAUCACCCAAACAU -2.1 -1.1 1 2 1 3 -35.1 77.5 -4 7 II 36.8 61.9 73.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0664 NM_003347 Huesken UBE2L3 7332 UUUGGGUGAUAGAUCUUUGuu CAAAGAUCUAUCACCCAAA -2.1 -0.9 1 1 4 3 -33.6 81.2 2 7 Ib 36.8 72.9 82.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0665 NM_003347 Huesken UBE2L3 7332 GGGUGAUAGAUCUUUGUUUua AAACAAAGAUCUAUCACCC -0.9 -3.3 1 2 -2 3 -33.7 70.4 -4 4 III 36.8 40.5 50.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0666 NM_003347 Huesken UBE2L3 7332 AUAGAUCUUUGUUUUAAAUgu AUUUAAAACAAAGAUCUAU -1.1 -1.1 2.8 1 2 1 -25.5 97.7 4.1 5 II 15.8 57.9 65.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0667 NM_003347 Huesken UBE2L3 7332 UUUUAAAUGUGAUCUUCGGug CCGAAGAUCACAUUUAAAA -3.3 -0.9 1.5 1 5 3 -30.3 89.1 2.7 8 Ia 31.6 72.4 83.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0668 NM_003347 Huesken UBE2L3 7332 UGAUCUUCGGUGGUUUGAAug UUCAAACCACCGAAGAUCA -0.9 -2.1 0.5 2 1 3 -36.1 71.6 -1.4 6 II 42.1 51.9 65.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0669 NM_003347 Huesken UBE2L3 7332 UCGGUGGUUUGAAUGGGUAcu UACCCAUUCAAACCACCGA -1.3 -2.4 2 0 0 3 -38.4 54.4 -4 5 II 47.4 49.5 71.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0670 NM_003347 Huesken UBE2L3 7332 UUGAAUGGGUACUCUGCUGga CAGCAGAGUACCCAUUCAA -2.1 -0.9 -1 1 3 3 -38.1 71.5 2.7 6 Ia 47.4 69 90 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0671 NM_003347 Huesken UBE2L3 7332 UCUGAAGGCUCCCUUAUCAua UGAUAAGGGAGCCUUCAGA -2.1 -2.4 -1 1 1 3 -39.7 60.5 -1 6 II 47.4 53.3 109.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0672 NM_003347 Huesken UBE2L3 7332 CUCCCUUAUCAUAUGGAGGgu CCUCCAUAUGAUAAGGGAG -3.3 -2.1 -3 1 1 3 -37.7 73.1 3.1 1 II 47.4 55.3 81.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0673 NM_003347 Huesken UBE2L3 7332 AUAUGGAGGGUUGUCAGGAac UCCUGACAACCCUCCAUAU -2.4 -1.1 2 2 3 3 -39.7 55.1 1.6 6 II 47.4 56.2 69.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0674 NM_003347 Huesken UBE2L3 7332 GGAACAAUAAGCCCUUGCCaa GGCAAGGGCUUAUUGUUCC -3.3 -3.3 -1.9 0 2 4 -39 63.7 7.5 3 II 52.6 49.8 79.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0675 NM_003347 Huesken UBE2L3 7332 UAAGCCCUUGCCAAGUCAAua UUGACUUGGCAAGGGCUUA -0.9 -1.3 -1.1 0 1 4 -38.8 59.2 -11 4 II 47.4 53.4 61.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0676 NM_003347 Huesken UBE2L3 7332 AAGCCCUUGCCAAGUCAAUaa AUUGACUUGGCAAGGGCUU -1.1 -0.9 -1.1 3 0 4 -38.6 54.4 -8.9 3 II 47.4 44.7 58.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0677 NM_003347 Huesken UBE2L3 7332 AGCCCUUGCCAAGUCAAUAaa UAUUGACUUGGCAAGGGCU -1.3 -2.1 -1 4 -1 4 -39 59.9 0.9 2 II 47.4 44.7 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0678 NM_003347 Huesken UBE2L3 7332 GCCAAGUCAAUAAAUUAGCuu GCUAAUUUAUUGACUUGGC -3.4 -3.4 -1.3 1 0 3 -32.4 64 7.5 3 II 36.8 52.6 46.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0679 NM_003347 Huesken UBE2L3 7332 AAUUAGCUUCAUCAACCUGga CAGGUUGAUGAAGCUAAUU -2.1 -0.9 -1.5 1 4 2 -33.4 75.8 10.4 5 Ia 36.8 61 96.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0680 NM_003347 Huesken UBE2L3 7332 UUAGCUUCAUCAACCUGGAug UCCAGGUUGAUGAAGCUAA -2.4 -0.9 -1.5 1 2 2 -37.1 69.3 -8.7 5 II 42.1 63.7 111.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0681 NM_003347 Huesken UBE2L3 7332 AUCAACCUGGAUGUUACGGaa CCGUAACAUCCAGGUUGAU -3.3 -1.1 -0.6 2 5 3 -37.4 70.9 10.4 5 Ib 47.4 60.2 61.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0682 NM_003344 Huesken UBE2H 7328 UGAGCUGUCCCCGGUACCCuc GGGUACCGGGGACAGCUCA -3.3 -2.1 -1.8 0 4 6 -46.7 46 2.7 3 II 68.4 63.8 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0683 NM_003344 Huesken UBE2H 7328 GAGCUGUCCCCGGUACCCUcu AGGGUACCGGGGACAGCUC -2.1 -2.4 -0.3 3 1 6 -46.7 38.4 -4 2 III 68.4 42 77.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0684 NM_003344 Huesken UBE2H 7328 GCUGUCCCCGGUACCCUCUuc AGAGGGUACCGGGGACAGC -2.1 -3.4 0.5 1 -1 6 -46.7 44.5 -3.5 2 III 68.4 35.8 65 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0685 NM_003344 Huesken UBE2H 7328 CCCCGGUACCCUCUUCCUGuu CAGGAAGAGGGUACCGGGG -2.1 -3.3 0.1 2 0 6 -45.3 41.1 3.4 0 II 68.4 39.3 74.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0686 NM_003344 Huesken UBE2H 7328 UUCCUGUUCUUUCAGCGCCuc GGCGCUGAAAGAACAGGAA -3.3 -0.9 -1.4 3 4 5 -39.3 72.7 12.8 5 Ib 52.6 75.3 98.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0687 NM_003344 Huesken UBE2H 7328 UUCUUUCAGCGCCUCCUCCgu GGAGGAGGCGCUGAAAGAA -3.3 -0.9 1.3 1 4 5 -41.9 75 9.8 6 Ia 57.9 70.9 91.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0688 NM_003344 Huesken UBE2H 7328 CAGCGCCUCCUCCGUGGCGua CGCCACGGAGGAGGCGCUG -2.4 -2.1 -5.4 0 1 5 -48.1 27.2 -2 -1 II 78.9 38.9 66.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0689 NM_003344 Huesken UBE2H 7328 AGCGCCUCCUCCGUGGCGUau ACGCCACGGAGGAGGCGCU -2.2 -2.1 -5.9 3 2 5 -48.2 40.6 -6.3 1 II 73.7 41.3 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0690 NM_003344 Huesken UBE2H 7328 CGUAUUUCUGGAUGUACUCuu GAGUACAUCCAGAAAUACG -2.4 -2.4 1 -1 0 2 -34.5 73.3 5.4 4 II 42.1 52.8 77.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0691 NM_003344 Huesken UBE2H 7328 GGAUGUACUCUUUAAUUUUcu AAAAUUAAAGAGUACAUCC -0.9 -3.3 1.1 0 -2 2 -29 78.4 -1 4 II 26.3 45.2 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0692 NM_003344 Huesken UBE2H 7328 UGUACUCUUUAAUUUUCUGcu CAGAAAAUUAAAGAGUACA -2.1 -2.1 2.5 0 4 1 -28.8 99.9 4.6 5 Ib 26.3 66.6 78.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0693 NM_003344 Huesken UBE2H 7328 UAAUUUUCUGCUUGUAUUCuu GAAUACAAGCAGAAAAUUA -2.4 -1.3 3.1 0 3 2 -29 103.8 8.1 9 Ia 26.3 79.7 93.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0694 NM_003344 Huesken UBE2H 7328 UUUUCUGCUUGUAUUCUUCug GAAGAAUACAAGCAGAAAA -2.4 -0.9 0 4 2 -31.1 101.6 10.2 8 Ia 31.6 76 95.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0695 NM_003344 Huesken UBE2H 7328 UUCUGCUUGUAUUCUUCUGgu CAGAAGAAUACAAGCAGAA -2.1 -0.9 2 3 2 -33.5 94.4 5.3 6 Ib 36.8 68.9 77.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0696 NM_003344 Huesken UBE2H 7328 UCUGCUUGUAUUCUUCUGGuc CCAGAAGAAUACAAGCAGA -3.3 -2.4 1 4 2 -35.9 87.7 7.8 7 Ib 42.1 73.1 103.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0697 NM_003344 Huesken UBE2H 7328 CUUGUAUUCUUCUGGUCGGug CCGACCAGAAGAAUACAAG -3.3 -2.1 0 2 3 -36.2 65.9 -4.4 4 II 47.4 53.6 86.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0698 NM_003344 Huesken UBE2H 7328 GUAUUCUUCUGGUCGGUGGag CCACCGACCAGAAGAAUAC -3.3 -2.2 2 2 3 -38.7 76 0 6 II 52.6 53.4 82.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0699 NM_003344 Huesken UBE2H 7328 UCUGGUCGGUGGAGGUACAug UGUACCUCCACCGACCAGA -2.1 -2.4 2.1 0 0 3 -43.4 41.6 -6.3 3 II 57.9 42.8 95.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0700 NM_003344 Huesken UBE2H 7328 CGGUGGAGGUACAUGGCUGca CAGCCAUGUACCUCCACCG -2.1 -2.4 1.8 0 0 3 -43 40.8 -2.3 1 II 63.2 41.7 61.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0701 NM_003344 Huesken UBE2H 7328 GGUACAUGGCUGCAGCGUCac GACGCUGCAGCCAUGUACC -2.4 -3.3 -1.2 2 1 3 -43.2 43.8 9.8 1 II 63.2 40.2 55.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0702 NM_003344 Huesken UBE2H 7328 ACAUGGCUGCAGCGUCACCau GGUGACGCUGCAGCCAUGU -3.3 -2.2 -1.9 1 3 3 -44 43.3 12.1 2 II 63.2 49.4 91 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0703 NM_003344 Huesken UBE2H 7328 AUGGCUGCAGCGUCACCAUug AUGGUGACGCUGCAGCCAU -1.1 -1.1 -2.9 1 1 3 -42.9 50.8 -6.3 2 II 57.9 48.2 86.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0704 NM_003344 Huesken UBE2H 7328 UGAGAGGAUCUAUGGGGUUag AACCCCAUAGAUCCUCUCA -0.9 -2.1 1 -1 1 4 -39.9 45.5 -1.3 6 II 47.4 52.5 49.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0705 NM_003344 Huesken UBE2H 7328 GAGGAUCUAUGGGGUUAGGau CCUAACCCCAUAGAUCCUC -3.3 -2.4 0.3 -1 1 4 -40 47.5 2.7 2 II 52.6 36.8 66.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0706 NM_003344 Huesken UBE2H 7328 GAUCUAUGGGGUUAGGAUAgg UAUCCUAACCCCAUAGAUC -1.3 -2.4 0.3 3 -2 4 -37 64.3 -0.7 4 II 42.1 38 50.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0707 NM_003344 Huesken UBE2H 7328 GGGGUUAGGAUAGGCCAAUaa AUUGGCCUAUCCUAACCCC -1.1 -3.3 0.4 0 -3 4 -40.7 36.2 -4 3 III 52.6 32.5 36.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0708 NM_003344 Huesken UBE2H 7328 AGGAUAGGCCAAUAACUGAgg UCAGUUAUUGGCCUAUCCU -2.4 -2.1 0.6 2 -1 4 -37.4 58.4 -1.5 6 II 42.1 46.7 66.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0709 NM_003344 Huesken UBE2H 7328 AGGCAGGAAGGACUCAAAUau AUUUGAGUCCUUCCUGCCU -1.1 -2.1 1.7 2 0 3 -39.1 49.1 3.5 4 II 47.4 43.2 48.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0710 NM_003344 Huesken UBE2H 7328 GGAAGGACUCAAAUAUAUUgg AAUAUAUUUGAGUCCUUCC -0.9 -3.3 2.4 0 -1 2 -31.8 62.2 -1.9 3 III 31.6 42.8 41.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0711 NM_003344 Huesken UBE2H 7328 GAAGGACUCAAAUAUAUUGgu CAAUAUAUUUGAGUCCUUC -2.1 -2.4 0.4 1 1 2 -30.6 73.2 2.3 4 II 31.6 54.1 84.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0712 NM_003344 Huesken UBE2H 7328 GGACUCAAAUAUAUUGGUAag UACCAAUAUAUUUGAGUCC -1.3 -3.3 0.1 1 -1 2 -32 68.8 1.3 3 III 31.6 34.9 48.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0713 NM_003344 Huesken UBE2H 7328 CAAAUAUAUUGGUAAGAUCau GAUCUUACCAAUAUAUUUG -2.4 -2.1 1.2 0 0 2 -28.5 81.3 5.4 5 II 26.3 58.7 78.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0714 NM_003344 Huesken UBE2H 7328 AAAUAUAUUGGUAAGAUCAua UGAUCUUACCAAUAUAUUU -2.1 -0.9 2 1 1 2 -28.5 91.5 -0.6 8 II 21.1 68.6 68.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0715 NM_003344 Huesken UBE2H 7328 UAUAUUGGUAAGAUCAUAGag CUAUGAUCUUACCAAUAUA -2.1 -1.3 1.7 0 4 2 -30.1 100 2 10 Ia 26.3 80 110 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0716 NM_003344 Huesken UBE2H 7328 UAAGAUCAUAGAGAGCUGUcc ACAGCUCUCUAUGAUCUUA -2.2 -1.3 0.8 0 2 2 -35.6 68 -1.3 8 II 36.8 67.3 95.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0717 NM_003344 Huesken UBE2H 7328 UCAUAGAGAGCUGUCCAAGuu CUUGGACAGCUCUCUAUGA -2.1 -2.4 -0.6 0 3 2 -38.6 62.3 5.7 7 Ia 47.4 61.7 81 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0718 NM_003344 Huesken UBE2H 7328 CAUAGAGAGCUGUCCAAGUuu ACUUGGACAGCUCUCUAUG -2.2 -2.1 -0.6 0 -1 2 -38.4 54.2 -6 4 II 47.4 45.9 86 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0719 NM_003344 Huesken UBE2H 7328 GUUUGAUUAAUUACAUCUAga UAGAUGUAAUUAAUCAAAC -1.3 -2.2 -0.9 1 -1 1 -27.2 83.7 -3.3 5 II 21.1 47.5 46.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0720 NM_003344 Huesken UBE2H 7328 UGAUUAAUUACAUCUAGACac GUCUAGAUGUAAUUAAUCA -2.2 -2.1 -0.9 0 3 1 -29.9 91.9 5.1 8 Ia 26.3 71.3 105.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0721 NM_003344 Huesken UBE2H 7328 ACAUCUAGACACACAGUUCcu GAACUGUGUGUCUAGAUGU -2.4 -2.2 0.4 1 2 1 -36.2 70.7 4.8 6 Ia 42.1 60.3 98.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0722 NM_003344 Huesken UBE2H 7328 AUCUAGACACACAGUUCCUga AGGAACUGUGUGUCUAGAU -2.1 -1.1 0.3 0 2 2 -37.3 63.7 -3.9 6 II 42.1 55.7 100.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0723 NM_003344 Huesken UBE2H 7328 AGACACACAGUUCCUGACGcu CGUCAGGAACUGUGUGUCU -2.4 -2.1 0.8 2 3 2 -39.5 58.7 8.1 5 Ib 52.6 60.2 99.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0724 NM_003344 Huesken UBE2H 7328 AUGGAAAAUUUUAUUCAUGaa CAUGAAUAAAAUUUUCCAU -2.1 -1.1 0.7 1 3 2 -26.4 80.9 5.5 5 Ia 21.1 67.6 64 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0725 NM_003344 Huesken UBE2H 7328 UUUUAUUCAUGAAUCCUAUag AUAGGAUUCAUGAAUAAAA -1.1 -0.9 1.8 1 2 2 -28.3 99.7 -1.5 9 II 21.1 69 106.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0726 NM_003344 Huesken UBE2H 7328 UUUAUUCAUGAAUCCUAUAga UAUAGGAUUCAUGAAUAAA -1.3 -0.9 1.8 0 0 2 -28.7 95.4 -1.5 7 II 21.1 66.1 67.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0727 NM_003344 Huesken UBE2H 7328 AUUCAUGAAUCCUAUAGAUgg AUCUAUAGGAUUCAUGAAU -1.1 -1.1 0.7 2 2 2 -31.2 76.7 -6 6 II 26.3 54.1 95.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0728 NM_003344 Huesken UBE2H 7328 AUCCUAUAGAUGGAGAUUUga AAAUCUCCAUCUAUAGGAU -0.9 -1.1 -1.5 4 0 2 -33.4 70.7 -4 6 II 31.6 59.2 96.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0729 NM_003344 Huesken UBE2H 7328 UGGAGAUUUGAAAGGGUAUuu AUACCCUUUCAAAUCUCCA -1.1 -2.1 5.1 0 -1 3 -34.8 65.8 -4.3 6 II 36.8 52.8 99.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0730 NM_003344 Huesken UBE2H 7328 AUUUGAAAGGGUAUUUAUCag GAUAAAUACCCUUUCAAAU -2.4 -1.1 1.4 2 4 3 -29.1 88.6 10.2 6 Ia 26.3 67.1 101.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0731 NM_003344 Huesken UBE2H 7328 AUUUAUCAGGUAGGUCCACuc GUGGACCUACCUGAUAAAU -2.2 -1.1 0 1 4 2 -36.3 58.6 10.1 6 Ia 42.1 55.6 77.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0732 NM_003344 Huesken UBE2H 7328 UUUAUCAGGUAGGUCCACUcu AGUGGACCUACCUGAUAAA -2.1 -0.9 0 1 3 2 -37.3 77.5 0.7 8 II 42.1 69.1 108.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0733 NM_003344 Huesken UBE2H 7328 GGUAGGUCCACUCUAACUUuc AAGUUAGAGUGGACCUACC -0.9 -3.3 0.3 2 0 2 -38.4 64.5 1.4 4 III 47.4 43.1 64.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0734 NM_003344 Huesken UBE2H 7328 GUAGGUCCACUCUAACUUUcc AAAGUUAGAGUGGACCUAC -0.9 -2.2 0.3 0 -1 2 -36 56.5 -6.3 3 III 42.1 43.6 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0735 NM_003344 Huesken UBE2H 7328 ACUCUAACUUUCCAUACUCcg GAGUAUGGAAAGUUAGAGU -2.4 -2.2 2.7 2 3 2 -34 67.7 7.5 5 Ia 36.8 60.2 83.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0736 NM_003344 Huesken UBE2H 7328 AUACUCCGCCUUCAUAUGGug CCAUAUGAAGGCGGAGUAU -3.3 -1.1 0.6 3 4 5 -37.9 68.2 5.4 6 Ib 47.4 63.5 101.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0737 NM_003344 Huesken UBE2H 7328 UCCGCCUUCAUAUGGUGUUcc AACACCAUAUGAAGGCGGA -0.9 -2.4 0.1 1 0 5 -38.6 66.2 -4 5 II 47.4 53.6 67.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0738 NM_003344 Huesken UBE2H 7328 CUUCAUAUGGUGUUCCUUGug CAAGGAACACCAUAUGAAG -2.1 -2.1 -0.7 1 1 2 -34.6 73.9 3 5 II 42.1 60.2 99.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0739 NM_003344 Huesken UBE2H 7328 GGUGUUCCUUGUGGUCCAUaa AUGGACCACAAGGAACACC -1.1 -3.3 -0.8 -1 -1 2 -40.2 47.4 -1 2 III 52.6 23.5 34 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0740 NM_003344 Huesken UBE2H 7328 UGUUCCUUGUGGUCCAUAAaa UUAUGGACCACAAGGAACA -0.9 -2.1 -0.8 2 -1 2 -36.9 83.6 -3.8 7 II 42.1 50 91.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0741 NM_003344 Huesken UBE2H 7328 GUGGUCCAUAAAACUUCACua GUGAAGUUUUAUGGACCAC -2.2 -2.2 0.5 0 1 2 -34.6 64.2 7.1 3 II 42.1 48.4 63.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0742 NM_003344 Huesken UBE2H 7328 UGGUCCAUAAAACUUCACUac AGUGAAGUUUUAUGGACCA -2.1 -2.1 0.5 0 1 2 -34.5 87.2 3.1 6 II 36.8 64.9 95.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0743 NM_003344 Huesken UBE2H 7328 UCCAUAAAACUUCACUACAaa UGUAGUGAAGUUUUAUGGA -2.1 -2.4 1.1 0 -1 2 -32.5 75.4 1.7 6 II 31.6 58.8 75.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0744 NM_003344 Huesken UBE2H 7328 AAAACUUCACUACAAAUUCau GAAUUUGUAGUGAAGUUUU -2.4 -0.9 0 2 3 1 -28.5 87.7 9.8 7 Ia 26.3 74 96.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0745 NM_003344 Huesken UBE2H 7328 CCUCCCAGGAUCGUAACCUca AGGUUACGAUCCUGGGAGG -2.1 -3.3 -1.2 1 0 3 -42.2 45.2 -6 1 III 57.9 43.2 84.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0746 NM_003344 Huesken UBE2H 7328 CUCCCAGGAUCGUAACCUCau GAGGUUACGAUCCUGGGAG -2.4 -2.1 -1.6 0 0 3 -41.3 44 3.1 0 II 57.9 42.8 57.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0747 NM_003344 Huesken UBE2H 7328 CCCAGGAUCGUAACCUCAUgu AUGAGGUUACGAUCCUGGG -1.1 -3.3 -1.6 0 -3 3 -40 42.6 -8.6 1 III 52.6 37.6 77.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0748 NM_003344 Huesken UBE2H 7328 AACCUCAUGUUUACUCUCGau CGAGAGUAAACAUGAGGUU -2.4 -0.9 1.3 3 3 2 -35.1 75.7 0.4 6 Ib 42.1 66.1 98 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0749 NM_003344 Huesken UBE2H 7328 CCUCAUGUUUACUCUCGAUga AUCGAGAGUAAACAUGAGG -1.1 -3.3 2.3 0 -2 2 -35.5 62.4 -3.3 3 III 42.1 34.8 71.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0750 NM_003344 Huesken UBE2H 7328 CUCAUGUUUACUCUCGAUGag CAUCGAGAGUAAACAUGAG -2.1 -2.1 2.2 0 0 2 -34.3 82.1 3.4 5 II 42.1 60.1 70.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0751 NM_003344 Huesken UBE2H 7328 UCAUGUUUACUCUCGAUGAgc UCAUCGAGAGUAAACAUGA -2.4 -2.4 1.4 1 0 2 -34.6 81.4 -6.1 7 II 36.8 62.1 71.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0752 NM_003345 Huesken UBE2I 7329 UUUGGCAGUAAAUCGUGUAgg UACACGAUUUACUGCCAAA -1.3 -0.9 2.4 0 1 3 -33.8 75.7 -1.5 7 II 36.8 62.5 92.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0753 NM_003345 Huesken UBE2I 7329 GGCAGUAAAUCGUGUAGGCcu GCCUACACGAUUUACUGCC -3.4 -3.3 1.9 -1 1 3 -38.7 51.3 5.1 2 II 52.6 38.9 67.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0754 NM_003345 Huesken UBE2I 7329 UAAAUCGUGUAGGCCUCUGcu CAGAGGCCUACACGAUUUA -2.1 -1.3 1.5 1 4 4 -37.6 70.7 2.3 8 Ia 47.4 69.2 83.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0755 NM_003345 Huesken UBE2I 7329 GUAGGCCUCUGCUUGAGCUgg AGCUCAAGCAGAGGCCUAC -2.1 -2.2 -1.9 1 2 4 -42.8 54.8 -4 0 III 57.9 42.1 89.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0756 NM_003345 Huesken UBE2I 7329 CUGCUUGAGCUGGGUCUUGga CAAGACCCAGCUCAAGCAG -2.1 -2.1 -1.4 0 -1 3 -41.1 41.3 -2 2 II 57.9 44.9 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0757 NM_003345 Huesken UBE2I 7329 UGGGUCUUGGAUAUUUGGUuc ACCAAAUAUCCAAGACCCA -2.2 -2.1 3 2 2 3 -37 79 1.1 5 II 42.1 60.6 83.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0758 NM_003345 Huesken UBE2I 7329 GGGUCUUGGAUAUUUGGUUca AACCAAAUAUCCAAGACCC -0.9 -3.3 3 2 -1 3 -35.8 70 -1.6 3 III 42.1 40.8 48.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0759 NM_003345 Huesken UBE2I 7329 UAUUUGGUUCAUUUAGAAGuu CUUCUAAAUGAACCAAAUA -2.1 -1.3 0.2 0 4 2 -28.9 101.7 7.7 8 Ia 26.3 71.5 88.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0760 NM_003345 Huesken UBE2I 7329 CAUUUAGAAGUUCCUGUAUuc AUACAGGAACUUCUAAAUG -1.1 -2.1 0.9 -1 -2 2 -31.4 77.5 -0.6 6 II 31.6 42.9 52.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0761 NM_003345 Huesken UBE2I 7329 AGUUCCUGUAUUCCUAAUAgg UAUUAGGAAUACAGGAACU -1.3 -2.1 2.4 2 -1 2 -33 85.7 1.7 6 II 31.6 51.8 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0762 NM_003345 Huesken UBE2I 7329 UGUAUUCCUAAUAGGAUCUgu AGAUCCUAUUAGGAAUACA -2.1 -2.1 -2.4 -1 1 2 -33.4 89.6 -1.2 7 II 31.6 66.5 90.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0763 NM_003345 Huesken UBE2I 7329 GUAUUCCUAAUAGGAUCUGuu CAGAUCCUAUUAGGAAUAC -2.1 -2.2 -2.4 -1 2 2 -33.4 63.9 0 4 II 36.8 48.2 74.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0764 NM_003345 Huesken UBE2I 7329 UAGGAUCUGUUUGAUUGUGau CACAAUCAAACAGAUCCUA -2.1 -1.3 0.7 1 3 2 -33.7 71.4 5.7 5 Ib 36.8 64.8 87.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0765 NM_003345 Huesken UBE2I 7329 CUGUUUGAUUGUGAUGGCUgg AGCCAUCACAAUCAAACAG -2.1 -2.1 4.4 -1 -1 3 -35.5 66.6 -3 4 II 42.1 47.9 60.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0766 NM_003345 Huesken UBE2I 7329 GUUUGAUUGUGAUGGCUGGcc CCAGCCAUCACAAUCAAAC -3.3 -2.2 4.4 1 2 3 -36.7 64.4 0 5 II 47.4 46.2 56 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0767 NM_003345 Huesken UBE2I 7329 UGGCCUCCAGUCCUUGUCCuc GGACAAGGACUGGAGGCCA -3.3 -2.1 -0.9 1 3 4 -45 61.5 9.8 3 II 63.2 63 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0768 NM_003345 Huesken UBE2I 7329 UCCAGUCCUUGUCCUCCUCua GAGGAGGACAAGGACUGGA -2.4 -2.4 0.5 0 2 2 -43.1 62.5 12.8 3 II 57.9 56 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0769 NM_003345 Huesken UBE2I 7329 UCUAAGAUGGACAGGCACAcu UGUGCCUGUCCAUCUUAGA -2.1 -2.4 0.3 0 0 3 -39.6 55.5 -3.7 7 II 47.4 56.8 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0770 NM_003345 Huesken UBE2I 7329 AAGAUGGACAGGCACACUGuc CAGUGUGCCUGUCCAUCUU -2.1 -0.9 -0.2 2 3 3 -40.2 60.5 2.4 7 Ib 52.6 66 80.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0771 NM_003345 Huesken UBE2I 7329 AGAUGGACAGGCACACUGUcc ACAGUGUGCCUGUCCAUCU -2.2 -2.1 -1.4 1 1 3 -41.5 50.7 -8.9 5 II 52.6 51.3 59.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0772 NM_003345 Huesken UBE2I 7329 GGACAGGCACACUGUCCCCga GGGGACAGUGUGCCUGUCC -3.3 -3.3 -7.5 0 2 4 -46.1 33.9 10.1 1 II 68.4 41.5 47.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0773 NM_003345 Huesken UBE2I 7329 GGCACACUGUCCCCGAAGGgu CCUUCGGGGACAGUGUGCC -3.3 -3.3 -3.8 1 0 5 -45.1 40.1 -2.3 -1 II 68.4 31.2 51.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0774 NM_003345 Huesken UBE2I 7329 UCCCCGAAGGGUACACAUUcg AAUGUGUACCCUUCGGGGA -0.9 -2.4 -7.4 2 -1 5 -40.8 51.3 -3.5 3 II 52.6 50.6 59.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0775 NM_003345 Huesken UBE2I 7329 CCCGAAGGGUACACAUUCGgg CGAAUGUGUACCCUUCGGG -2.4 -3.3 -2.8 0 -1 4 -39.9 38.5 -1.9 1 II 57.9 40.3 45.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0776 NM_003345 Huesken UBE2I 7329 GGGUACACAUUCGGGUGAAau UUCACCCGAAUGUGUACCC -0.9 -3.3 -0.4 -1 -3 4 -39.7 37.5 -3.4 3 III 52.6 19 49.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0777 NM_003345 Huesken UBE2I 7329 UACACAUUCGGGUGAAAUAau UAUUUCACCCGAAUGUGUA -1.3 -1.3 -0.4 1 -1 4 -34.2 76.5 -3.8 6 II 36.8 55.2 78.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0778 NM_003345 Huesken UBE2I 7329 AUUCGGGUGAAAUAAUGGUgg ACCAUUAUUUCACCCGAAU -2.2 -1.1 0.5 3 3 4 -33.9 66.5 -1.7 6 II 36.8 58.8 88.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0779 NM_003345 Huesken UBE2I 7329 GAAAUAAUGGUGGUUCGAAuu UUCGAACCACCAUUAUUUC -0.9 -2.4 2.7 1 0 2 -32.8 60.2 -1.4 5 II 36.8 38.9 59.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0780 NM_003345 Huesken UBE2I 7329 AAAUAAUGGUGGUUCGAAUuu AUUCGAACCACCAUUAUUU -1.1 -0.9 3.8 3 2 2 -31.5 78.8 1.1 7 II 31.6 52.8 81 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0781 NM_003345 Huesken UBE2I 7329 AAUGGUGGUUCGAAUUUACau GUAAAUUCGAACCACCAUU -2.2 -0.9 2.1 1 3 2 -32.6 69.1 2.5 6 Ib 36.8 60 89.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0782 NM_003345 Huesken UBE2I 7329 UGGUGGUUCGAAUUUACAUuu AUGUAAAUUCGAACCACCA -1.1 -2.1 1.9 2 1 2 -33.8 81.3 0.7 5 II 36.8 59.4 75 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0783 NM_003345 Huesken UBE2I 7329 GUGGUUCGAAUUUACAUUUug AAAUGUAAAUUCGAACCAC -0.9 -2.2 1.9 0 -2 2 -30.2 77.4 -1 4 III 31.6 50.1 53.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0784 NM_003345 Huesken UBE2I 7329 UUCGAAUUUACAUUUUGGUgg ACCAAAAUGUAAAUUCGAA -2.2 -0.9 1.9 1 3 2 -28.9 90.7 -1.3 7 II 26.3 69.1 86.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0785 NM_003345 Huesken UBE2I 7329 UGGCGAAGAUGGAUAAUCAuc UGAUUAUCCAUCUUCGCCA -2.1 -2.1 0.8 1 0 4 -36.8 58.6 -4 5 II 42.1 52.5 59 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0786 NM_003345 Huesken UBE2I 7329 CGAAGAUGGAUAAUCAUCUuu AGAUGAUUAUCCAUCUUCG -2.1 -2.4 -3.4 1 -1 2 -33.6 63.8 -6.2 4 II 36.8 54.6 52.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0787 NM_003345 Huesken UBE2I 7329 AUGGAUAAUCAUCUUUGAAaa UUCAAAGAUGAUUAUCCAU -0.9 -1.1 0.5 1 1 2 -30.6 82.1 9 5 II 26.3 52.2 65.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0788 NM_003345 Huesken UBE2I 7329 CAUCUUUGAAAAGCAUCCGua CGGAUGCUUUUCAAAGAUG -2.4 -2.1 -0.3 1 2 3 -33.5 71.3 0.3 5 II 42.1 61.1 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0789 NM_003345 Huesken UBE2I 7329 AAAAGCAUCCGUAGUUUAAac UUAAACUACGGAUGCUUUU -0.9 -0.9 2.9 1 0 3 -31.3 75.6 -3.3 7 II 31.6 49.2 50.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0790 NM_003345 Huesken UBE2I 7329 AGCAUCCGUAGUUUAAACAag UGUUUAAACUACGGAUGCU -2.1 -2.1 1.2 1 0 3 -33.8 80 1.6 5 II 36.8 49.8 68.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0791 NM_003345 Huesken UBE2I 7329 AUCCGUAGUUUAAACAAGCcu GCUUGUUUAAACUACGGAU -3.4 -1.1 0.6 2 3 3 -32.6 64.1 4.8 4 Ib 36.8 69.3 92.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0792 NM_003345 Huesken UBE2I 7329 CGUAGUUUAAACAAGCCUCcu GAGGCUUGUUUAAACUACG -2.4 -2.4 1.2 0 0 3 -33.6 72.3 2.8 4 II 42.1 58.5 73.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0793 NM_003345 Huesken UBE2I 7329 GUAGUUUAAACAAGCCUCCuu GGAGGCUUGUUUAAACUAC -3.3 -2.2 1.5 0 2 3 -34.5 66.3 2.5 6 II 42.1 63.9 82.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0794 NM_003345 Huesken UBE2I 7329 UAAACAAGCCUCCUUCCCAcg UGGGAAGGAGGCUUGUUUA -2.1 -1.3 0.6 1 3 3 -39 67.8 -1.4 7 II 47.4 65.8 78 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0795 NM_003345 Huesken UBE2I 7329 CAAGCCUCCUUCCCACGGAgu UCCGUGGGAAGGAGGCUUG -2.4 -2.1 -2.3 1 -1 3 -44 43.1 -5.7 1 III 63.2 39.7 52.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0796 NM_003345 Huesken UBE2I 7329 UCCUUCCCACGGAGUCCCUuu AGGGACUCCGUGGGAAGGA -2.1 -2.4 -1.6 -1 1 3 -45.5 48.8 -6.6 3 II 63.2 45.8 72.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0797 NM_003345 Huesken UBE2I 7329 UUCCCACGGAGUCCCUUUCuu GAAAGGGACUCCGUGGGAA -2.4 -0.9 -0.8 2 2 3 -41.9 66.5 12.8 5 II 57.9 61.1 89.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0798 NM_003345 Huesken UBE2I 7329 UCCCACGGAGUCCCUUUCUuu AGAAAGGGACUCCGUGGGA -2.1 -2.4 -0.8 1 0 3 -43.1 51.6 -1.2 5 II 57.9 52.3 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0799 NM_003345 Huesken UBE2I 7329 CCCACGGAGUCCCUUUCUUuc AAGAAAGGGACUCCGUGGG -0.9 -3.3 -0.8 0 -2 3 -41.6 44.9 -5.9 1 III 57.9 30.5 45.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0800 NM_003345 Huesken UBE2I 7329 CACGGAGUCCCUUUCUUUCcu GAAAGAAAGGGACUCCGUG -2.4 -2.1 -0.8 0 0 3 -38.3 64.5 8.4 3 II 52.6 49.4 53.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0801 NM_003345 Huesken UBE2I 7329 GAGUCCCUUUCUUUCCUGGaa CCAGGAAAGAAAGGGACUC -3.3 -2.4 0.4 0 2 3 -39.1 73.5 3 3 II 52.6 45.8 54.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0802 NM_003345 Huesken UBE2I 7329 UCCCUUUCUUUCCUGGAAUgg AUUCCAGGAAAGAAAGGGA -1.1 -2.4 -0.9 2 0 3 -36.8 73.9 -1.6 5 II 42.1 53.8 83.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0803 NM_003345 Huesken UBE2I 7329 UUCCUGGAAUGGCGCACUCcc GAGUGCGCCAUUCCAGGAA -2.4 -0.9 -1.6 0 3 5 -41.9 52.6 9.8 4 II 57.9 60.9 72.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0804 NM_003345 Huesken UBE2I 7329 GCACUCCCAGUUCAUGAGGuu CCUCAUGAACUGGGAGUGC -3.3 -3.4 -1.8 1 1 3 -41.6 47.2 5.4 0 II 57.9 39.8 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0805 NM_003345 Huesken UBE2I 7329 CACUCCCAGUUCAUGAGGUuc ACCUCAUGAACUGGGAGUG -2.2 -2.1 -1.8 0 0 3 -40.4 55 -8.6 1 III 52.6 38.2 58.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0806 NM_003345 Huesken UBE2I 7329 ACUCCCAGUUCAUGAGGUUca AACCUCAUGAACUGGGAGU -0.9 -2.2 -1.8 1 1 3 -39.2 49.5 -6.3 3 II 47.4 38.9 34.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0807 NM_003345 Huesken UBE2I 7329 CAGUUCAUGAGGUUCAUCGug CGAUGAACCUCAUGAACUG -2.4 -2.1 -0.3 0 1 2 -36.3 82.3 0.3 6 II 47.4 62.9 78.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0808 NM_003345 Huesken UBE2I 7329 UUCAUGAGGUUCAUCGUGCca GCACGAUGAACCUCAUGAA -3.4 -0.9 -0.3 1 4 2 -37.6 72.4 4.8 8 Ia 47.4 75.9 84.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0809 NM_003345 Huesken UBE2I 7329 AGGUUCAUCGUGCCAUCGGga CCGAUGGCACGAUGAACCU -3.3 -2.1 0.5 2 3 3 -41.2 59 2.4 4 Ib 57.9 57 81.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0810 NM_003345 Huesken UBE2I 7329 GGUUCAUCGUGCCAUCGGGau CCCGAUGGCACGAUGAACC -3.3 -3.3 0.5 2 2 4 -42.4 50.3 0.1 2 II 63.2 37.7 55 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0811 NM_003345 Huesken UBE2I 7329 GUUCAUCGUGCCAUCGGGAuu UCCCGAUGGCACGAUGAAC -2.4 -2.2 0.5 1 1 4 -41.5 43.5 -6 2 II 57.9 36.6 48.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0812 NM_003345 Huesken UBE2I 7329 GACAGCCACGAAACCAAAUgg AUUUGGUUUCGUGGCUGUC -1.1 -2.4 -0.7 1 -2 3 -36.9 51.8 -4.3 2 III 47.4 35.6 51.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0813 NM_003345 Huesken UBE2I 7329 GCCACGAAACCAAAUGGGUgg ACCCAUUUGGUUUCGUGGC -2.2 -3.4 -2 0 -1 3 -39 40.5 -8.9 1 III 52.6 33.1 56.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0814 NM_003345 Huesken UBE2I 7329 CCACGAAACCAAAUGGGUGgu CACCCAUUUGGUUUCGUGG -2.1 -3.3 -1.6 1 1 3 -37.7 42.8 0 1 II 52.6 44.4 85.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0815 NM_003345 Huesken UBE2I 7329 GAAACCAAAUGGGUGGUCUuu AGACCACCCAUUUGGUUUC -2.1 -2.4 -3.9 0 1 3 -37.7 63.9 -1.6 4 II 47.4 44.8 79.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0816 NM_014501 Huesken UBE2S 27338 UUCUUAUCGCGCUCGCCAGca CUGGCGAGCGCGAUAAGAA -2.1 -0.9 -1.5 2 3 5 -40.5 69.8 -2.4 5 Ia 57.9 62.8 82.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0817 NM_014501 Huesken UBE2S 27338 UUAUCGCGCUCGCCAGCAUgc AUGCUGGCGAGCGCGAUAA -1.1 -0.9 -2.3 1 2 5 -41.7 53.6 -3.9 4 II 57.9 50.4 71.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0818 NM_014501 Huesken UBE2S 27338 GCCAGCAUGCUUCUUGGCCau GGCCAAGAAGCAUGCUGGC -3.3 -3.4 -2.8 1 2 4 -43.5 51.9 15.2 0 II 63.2 43.5 57.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0819 NM_014501 Huesken UBE2S 27338 GCCAUGGGACCCUCAGCCCcu GGGCUGAGGGUCCCAUGGC -3.3 -3.4 -4.3 0 1 4 -48.5 34.8 2.7 1 II 73.7 40.3 45.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0820 NM_014501 Huesken UBE2S 27338 CCAUGGGACCCUCAGCCCCuc GGGGCUGAGGGUCCCAUGG -3.3 -3.3 -8.5 0 1 5 -48.4 33.6 8.5 1 II 73.7 47.4 42.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0821 NM_014501 Huesken UBE2S 27338 AUGGGACCCUCAGCCCCUCcc GAGGGGCUGAGGGUCCCAU -2.4 -1.1 -8.7 2 3 5 -47.5 32 5.1 1 II 68.4 51.7 45 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0822 NM_014501 Huesken UBE2S 27338 GGCCCCAGGGUCGGUGGAGga CUCCACCGACCCUGGGGCC -2.1 -3.3 -3.7 1 0 6 -49.8 16.6 -2.4 -1 II 78.9 23 44 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0823 NM_014501 Huesken UBE2S 27338 AGGGUCGGUGGAGGAAGCUuc AGCUUCCUCCACCGACCCU -2.1 -2.1 2.2 0 1 3 -45.3 29.9 -4 3 II 63.2 41.9 49.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0824 NM_014501 Huesken UBE2S 27338 GUGGAGGAAGCUUCAGUGCca GCACUGAAGCUUCCUCCAC -3.4 -2.2 -0.7 0 1 2 -41.5 48.9 10.8 3 II 57.9 48.7 58.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0825 NM_014501 Huesken UBE2S 27338 AAGCUUCAGUGCCACUGGCca GCCAGUGGCACUGAAGCUU -3.4 -0.9 -2.7 3 4 3 -42.2 54.5 7.5 2 Ib 57.9 56.2 57.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0826 NM_014501 Huesken UBE2S 27338 GUGCCACUGGCCAGGGCCCga GGGCCCUGGCCAGUGGCAC -3.3 -2.2 -5.7 1 2 6 -50.3 24.1 0.1 -1 II 78.9 39.1 43 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0827 NM_014501 Huesken UBE2S 27338 ACUGGCCAGGGCCCGACCGgc CGGUCGGGCCCUGGCCAGU -2.4 -2.2 -7.1 2 4 7 -49.9 31.2 0.1 1 II 78.9 48.4 41.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0828 NM_014501 Huesken UBE2S 27338 GGCCAGGGCCCGACCGGCUuc AGCCGGUCGGGCCCUGGCC -2.1 -3.3 -6.3 2 -1 7 -52.3 12 -6.2 0 III 84.2 27.5 43 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0829 NM_014501 Huesken UBE2S 27338 GCCCGACCGGCUUCGGCCCug GGGCCGAAGCCGGUCGGGC -3.3 -3.4 -7.3 2 1 6 -50.5 23.4 8.1 -2 II 84.2 31.7 36.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0830 NM_014501 Huesken UBE2S 27338 CCCGACCGGCUUCGGCCCUgc AGGGCCGAAGCCGGUCGGG -2.1 -3.3 -7.3 -1 -2 6 -49.2 17.5 2.2 -1 III 78.9 24.8 49.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0831 NM_014501 Huesken UBE2S 27338 UUCGGCCCUGCCGCUGGGCcc GCCCAGCGGCAGGGCCGAA -3.4 -0.9 -6.4 0 4 6 -49.9 35.5 2.7 2 II 78.9 57 42 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0832 NM_014501 Huesken UBE2S 27338 CGUGGAUCUCUGUGAGCAGac CUGCUCACAGAGAUCCACG -2.1 -2.4 -0.8 -1 0 2 -41 39.9 -2 1 II 57.9 36.2 54.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0833 NM_014501 Huesken UBE2S 27338 AUCUCUGUGAGCAGACGGGcc CCCGUCUGCUCACAGAGAU -3.3 -1.1 -2.6 1 4 4 -42.2 56.5 -4.9 4 Ib 57.9 57.9 70.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0834 NM_014501 Huesken UBE2S 27338 GUGAGCAGACGGGCCCGAGcu CUCGGGCCCGUCUGCUCAC -2.1 -2.2 -4.4 0 1 8 -46.9 31.2 0 1 II 73.7 36.9 55 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0835 NM_014501 Huesken UBE2S 27338 ACGGGCCCGAGCUGCAUACuc GUAUGCAGCUCGGGCCCGU -2.2 -2.2 -0.6 1 1 8 -45.8 40.1 5.1 3 II 68.4 43.7 47 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0836 NM_014501 Huesken UBE2S 27338 CGGGCCCGAGCUGCAUACUcc AGUAUGCAGCUCGGGCCCG -2.1 -2.4 -0.6 -1 -3 8 -45.7 32.8 -5.3 -1 III 68.4 28.8 49.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0837 NM_014501 Huesken UBE2S 27338 GGGCCCGAGCUGCAUACUCcu GAGUAUGCAGCUCGGGCCC -2.4 -3.3 -3.6 2 0 7 -45.7 32.9 9.8 -1 II 68.4 36.8 53.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0838 NM_014501 Huesken UBE2S 27338 CCCGAGCUGCAUACUCCUCgu GAGGAGUAUGCAGCUCGGG -2.4 -3.3 -3.6 0 -1 4 -43.5 40 10.8 -1 II 63.2 38.3 56.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0839 NM_014501 Huesken UBE2S 27338 CUGCAUACUCCUCGUAGUUcu AACUACGAGGAGUAUGCAG -0.9 -2.1 -0.3 -1 -2 2 -37.7 54.5 -0.2 3 II 47.4 41.4 40 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0840 NM_014501 Huesken UBE2S 27338 AUACUCCUCGUAGUUCUCCaa GGAGAACUACGAGGAGUAU -3.3 -1.1 -0.3 3 5 2 -38.2 68.7 9.7 6 Ib 47.4 69 56.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0841 NM_014501 Huesken UBE2S 27338 UCGUAGUUCUCCAAGAGCAgg UGCUCUUGGAGAACUACGA -2.1 -2.4 -0.1 2 0 2 -38.8 60.3 -8.3 6 II 47.4 58.1 77.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0842 NM_014501 Huesken UBE2S 27338 GUAGUUCUCCAAGAGCAGGcg CCUGCUCUUGGAGAACUAC -3.3 -2.2 -0.5 1 2 2 -39.4 53.4 2.3 3 II 52.6 51.5 70.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0843 NM_014501 Huesken UBE2S 27338 UAGUUCUCCAAGAGCAGGCgg GCCUGCUCUUGGAGAACUA -3.4 -1.3 -0.7 1 4 3 -40.6 74 7.1 8 Ia 52.6 74.5 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0844 NM_014501 Huesken UBE2S 27338 UCUCCAAGAGCAGGCGGCCcg GGCCGCCUGCUCUUGGAGA -3.3 -2.4 -0.7 0 4 7 -46.5 34.9 5.1 4 Ib 68.4 56.1 69.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0845 NM_014501 Huesken UBE2S 27338 AGGCGGCCCGCCUCCUCGUug ACGAGGAGGCGGGCCGCCU -2.2 -2.1 -5.4 3 1 11 -50.5 27.4 -8.7 0 II 78.9 39.7 44.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0846 NM_014501 Huesken UBE2S 27338 CCGCCUCCUCGUUGAGUGCag GCACUCAACGAGGAGGCGG -3.4 -3.3 -2.3 -1 -1 5 -44.5 43.7 8.4 -1 II 68.4 35.1 48.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0847 NM_014501 Huesken UBE2S 27338 CCUCGUUGAGUGCAGACUCgg GAGUCUGCACUCAACGAGG -2.4 -3.3 -2.9 1 0 2 -40.9 46.9 7.8 0 II 57.9 48.2 71.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0848 NM_014501 Huesken UBE2S 27338 CUCGUUGAGUGCAGACUCGgg CGAGUCUGCACUCAACGAG -2.4 -2.1 -3.2 -1 0 2 -40 45.7 -6.9 2 II 57.9 48.9 70.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0849 NM_014501 Huesken UBE2S 27338 GAGUGCAGACUCGGGGUUAgg UAACCCCGAGUCUGCACUC -1.3 -2.4 -1.5 -1 -3 5 -42.2 36.5 -6.1 2 III 57.9 28.4 39.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0850 NM_014501 Huesken UBE2S 27338 GACUCGGGGUUAGGGUGGAuc UCCACCCUAACCCCGAGUC -2.4 -2.4 2.3 0 -1 5 -44.5 27.2 -3.8 2 III 63.2 23.5 39.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0851 NM_014501 Huesken UBE2S 27338 GGGUGGAUCAGCAGGCACUug AGUGCCUGCUGAUCCACCC -2.1 -3.3 0.1 0 -2 3 -45 39.4 -8.9 2 III 63.2 37.7 55.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0852 NM_014501 Huesken UBE2S 27338 GUGGAUCAGCAGGCACUUGau CAAGUGCCUGCUGAUCCAC -2.1 -2.2 -0.2 1 0 3 -41.4 41.9 5 2 II 57.9 41.3 63.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0853 NM_014501 Huesken UBE2S 27338 GAUGGUCAGCAGUACGUGUcg ACACGUACUGCUGACCAUC -2.2 -2.4 1.7 1 0 2 -39.9 53.2 -1.7 3 III 52.6 39.9 59.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0854 NM_014501 Huesken UBE2S 27338 AUGGUCAGCAGUACGUGUCgg GACACGUACUGCUGACCAU -2.4 -1.1 1.7 2 3 2 -39.9 67.5 7.8 6 Ib 52.6 65.4 85.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0855 NM_014501 Huesken UBE2S 27338 GGAUGCCCAGCUCAGCCGUcc ACGGCUGAGCUGGGCAUCC -2.2 -3.3 -3 0 0 4 -46.5 36.4 -0.9 0 III 68.4 30.1 52.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0856 NM_014501 Huesken UBE2S 27338 CCUCUUGAGCACGUUGACGca CGUCAACGUGCUCAAGAGG -2.4 -3.3 0.7 1 1 2 -39.7 51.7 0.3 2 II 57.9 47 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0857 NM_014501 Huesken UBE2S 27338 UCUUGAGCACGUUGACGCAga UGCGUCAACGUGCUCAAGA -2.1 -2.4 -1.6 -1 1 3 -39.8 54.3 -0.7 5 II 52.6 45.5 74.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0858 NM_014501 Huesken UBE2S 27338 CUUGAGCACGUUGACGCAGau CUGCGUCAACGUGCUCAAG -2.1 -2.1 -1.6 0 1 3 -39.5 41.3 3.7 1 II 57.9 46.6 67.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0859 NM_014501 Huesken UBE2S 27338 GUUGACGCAGAUCUCGCCAuu UGGCGAGAUCUGCGUCAAC -2.1 -2.2 -4.2 0 1 4 -41.4 54.1 9 2 III 57.9 42 85.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0860 NM_014501 Huesken UBE2S 27338 UCUCGCCAUUGGCGCCCACgu GUGGGCGCCAAUGGCGAGA -2.2 -2.4 -4.7 0 3 7 -45.6 38.3 9.8 2 II 68.4 45.1 54.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0861 NM_014501 Huesken UBE2S 27338 CAUUGGCGCCCACGUUCGGgu CCGAACGUGGGCGCCAAUG -3.3 -2.1 -0.7 -1 2 7 -43.2 36.3 -2 2 II 68.4 39.2 44.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0862 NM_014501 Huesken UBE2S 27338 CCACGUUCGGGUGGAAGAUcu AUCUUCCACCCGAACGUGG -1.1 -3.3 -3.2 1 -2 4 -41 35.4 -3 0 III 57.9 29.3 31.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0863 NM_014501 Huesken UBE2S 27338 CGUUCGGGUGGAAGAUCUUgg AAGAUCUUCCACCCGAACG -0.9 -2.4 1.2 -2 -2 4 -38.8 41.2 -8.6 3 III 52.6 32.1 60.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0864 NM_014501 Huesken UBE2S 27338 UCUUGGUCAGGAAGUAGCCcu GGCUACUUCCUGACCAAGA -3.3 -2.4 0.4 0 4 3 -40.6 59.5 4.8 6 Ib 52.6 65.4 91.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0865 NM_014501 Huesken UBE2S 27338 AGGAAGUAGCCCUUGGGUGgg CACCCAAGGGCUACUUCCU -2.1 -2.1 -3.5 3 3 4 -42.4 54.3 0.3 3 Ib 57.9 53.9 81.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0866 NM_014501 Huesken UBE2S 27338 GGAAGUAGCCCUUGGGUGGgg CCACCCAAGGGCUACUUCC -3.3 -3.3 -1.8 0 1 4 -43.6 48.1 0.7 2 II 63.2 42.5 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0867 NM_014501 Huesken UBE2S 27338 AGUAGCCCUUGGGUGGGGAgg UCCCCACCCAAGGGCUACU -2.4 -2.1 -3.4 1 2 4 -46 43.1 -1.4 2 II 63.2 34.5 48.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0868 NM_014501 Huesken UBE2S 27338 AGCCCUUGGGUGGGGAGGCag GCCUCCCCACCCAAGGGCU -3.4 -2.1 -3.7 3 3 4 -49.2 32.5 7.4 1 II 73.7 47.4 46.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0869 NM_014501 Huesken UBE2S 27338 GGGGAGGCAGGGAAGUCCUuc AGGACUUCCCUGCCUCCCC -2.1 -3.3 -1.5 0 -1 4 -47.3 26.1 -3.9 0 III 68.4 34.5 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0870 NM_014501 Huesken UBE2S 27338 CAGGGAAGUCCUUCCCCAGca CUGGGGAAGGACUUCCCUG -2.1 -2.1 -8 -1 0 4 -43.6 42.3 -1.3 0 II 63.2 44 40.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0871 NM_014501 Huesken UBE2S 27338 AGGGAAGUCCUUCCCCAGCag GCUGGGGAAGGACUUCCCU -3.4 -2.1 -7.3 2 2 4 -44.9 45.9 15.5 2 II 63.2 54.8 53.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0872 NM_014501 Huesken UBE2S 27338 UUCCCCAGCAGGAGUUUCAug UGAAACUCCUGCUGGGGAA -2.1 -0.9 -4.9 1 0 4 -41.3 62.8 -6.3 6 II 52.6 57 54 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0873 NM_014501 Huesken UBE2S 27338 GAGUUUCAUGCGGAACAGAcc UCUGUUCCGCAUGAAACUC -2.4 -2.4 1 0 -2 4 -37.4 48.8 -6.1 3 II 47.4 35.5 42.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0874 NM_014501 Huesken UBE2S 27338 CAUGCGGAACAGACCUCCAgc UGGAGGUCUGUUCCGCAUG -2.1 -2.1 -2.7 -1 -1 4 -41.9 44.9 -6 1 III 57.9 42 58.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0875 NM_014501 Huesken UBE2S 27338 GACCUCCAGCAUAUGGGGUcc ACCCCAUAUGCUGGAGGUC -2.2 -2.4 -1.5 2 1 4 -43.1 51 1.1 0 III 57.9 33.5 49.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0876 NM_014501 Huesken UBE2S 27338 CCAGCAUAUGGGGUCCCCUca AGGGGACCCCAUAUGCUGG -2.1 -3.3 -2.8 0 0 4 -45.1 39 -3.6 0 III 63.2 41.3 36.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0877 NM_014501 Huesken UBE2S 27338 CAUAUGGGGUCCCCUCAGGgc CCUGAGGGGACCCCAUAUG -3.3 -2.1 -2.8 0 1 4 -44.1 47.6 -4.3 3 II 63.2 48.1 25.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0878 NM_014501 Huesken UBE2S 27338 AUAUGGGGUCCCCUCAGGGcc CCCUGAGGGGACCCCAUAU -3.3 -1.1 -3.9 1 6 4 -45.3 49.3 0 4 Ib 63.2 61.7 46.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0879 NM_014501 Huesken UBE2S 27338 GGGUCCCCUCAGGGCCCUCga GAGGGCCCUGAGGGGACCC -2.4 -3.3 -4.1 -1 0 6 -50.9 27.3 9.7 -1 II 78.9 28.4 44.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0880 NM_014501 Huesken UBE2S 27338 UCAGGGCCCUCGAUGGUGAcc UCACCAUCGAGGGCCCUGA -2.4 -2.4 -1 1 1 6 -45.7 40.3 -6.4 3 II 63.2 46.8 35.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0881 NM_014501 Huesken UBE2S 27338 CAGGGCCCUCGAUGGUGACcu GUCACCAUCGAGGGCCCUG -2.2 -2.1 -1 -2 0 6 -45.5 35.1 5.4 -1 II 68.4 33.7 45.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0882 NM_014501 Huesken UBE2S 27338 UGAGGUCCUCCUCGUUGGGaa CCCAACGAGGAGGACCUCA -3.3 -2.1 -5.3 -1 4 3 -44.3 48.2 3.1 2 II 63.2 53.7 54 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0883 NM_014501 Huesken UBE2S 27338 GAGGUCCUCCUCGUUGGGAaa UCCCAACGAGGAGGACCUC -2.4 -2.4 -3.6 1 0 3 -44.6 41.2 -3.8 0 III 63.2 31.5 35.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0884 NM_014501 Huesken UBE2S 27338 AGGUCCUCCUCGUUGGGAAag UUCCCAACGAGGAGGACCU -0.9 -2.1 -2.2 3 0 3 -43.1 60.5 -3.8 2 II 57.9 36.3 41.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0885 NM_014501 Huesken UBE2S 27338 GUCCUCCUCGUUGGGAAAGac CUUUCCCAACGAGGAGGAC -2.1 -2.2 -2.8 1 0 3 -40.7 47.5 3 0 II 57.9 36.2 33.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0886 NM_014501 Huesken UBE2S 27338 CCUCGUUGGGAAAGACCUUga AAGGUCUUUCCCAACGAGG -0.9 -3.3 -0.8 1 -2 3 -39.2 37.4 -6.3 2 III 52.6 35.4 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0887 NM_014501 Huesken UBE2S 27338 UGGGAAAGACCUUGAUGCCau GGCAUCAAGGUCUUUCCCA -3.3 -2.1 -1.2 -1 3 3 -40.3 54.3 10.8 4 Ib 52.6 59.1 57.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0888 NM_014501 Huesken UBE2S 27338 GGAAAGACCUUGAUGCCAUcg AUGGCAUCAAGGUCUUUCC -1.1 -3.3 -1.2 1 0 3 -38.1 49.6 -1.5 3 II 47.4 38.6 56.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0889 NM_014501 Huesken UBE2S 27338 GACCUUGAUGCCAUCGGGUgg ACCCGAUGGCAUCAAGGUC -2.2 -2.4 0 1 1 4 -42.1 47.3 -8.9 2 III 57.9 41.6 66.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0890 NM_014501 Huesken UBE2S 27338 CCUUGAUGCCAUCGGGUGGgu CCACCCGAUGGCAUCAAGG -3.3 -3.3 -0.3 0 0 4 -42.9 50 5.7 3 II 63.2 39.1 47.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0891 NM_014501 Huesken UBE2S 27338 UGAUGCCAUCGGGUGGGUCug GACCCACCCGAUGGCAUCA -2.4 -2.1 -0.6 0 4 4 -44.5 51.2 9.7 4 II 63.2 54.3 61.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0892 NM_014501 Huesken UBE2S 27338 GCCAUCGGGUGGGUCUGCGgu CGCAGACCCACCCGAUGGC -2.4 -3.4 -0.6 1 2 4 -46.8 35.7 2.3 2 II 73.7 35 51.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0893 NM_014501 Huesken UBE2S 27338 GGGUGGGUCUGCGGUCAGUgu ACUGACCGCAGACCCACCC -2.2 -3.3 -1.5 0 -2 4 -46.4 27.5 -6.3 0 III 68.4 24.4 43.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0894 NM_014501 Huesken UBE2S 27338 UGCGGUCAGUGUCGUCACCuc GGUGACGACACUGACCGCA -3.3 -2.1 -2.1 0 2 4 -43.5 49.1 12.8 1 II 63.2 52.9 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0895 NM_004223 Huesken UBE2L6 9246 UCCGAAUCGGAGGGUGAACuc GUUCACCCUCCGAUUCGGA -2.2 -2.4 -2 1 1 3 -41.5 44.4 12.4 3 Ib 57.9 49.5 61.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0896 NM_004223 Huesken UBE2L6 9246 CCGAAUCGGAGGGUGAACUcu AGUUCACCCUCCGAUUCGG -2.1 -3.3 -0.1 0 -2 3 -41.2 46.3 -0.9 2 III 57.9 39.2 55.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0897 NM_004223 Huesken UBE2L6 9246 CGGAGGGUGAACUCUUCGGca CCGAAGAGUUCACCCUCCG -3.3 -2.4 -1.1 0 0 3 -42.2 49.2 -2.1 1 II 63.2 46.8 62.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0898 NM_004223 Huesken UBE2L6 9246 GAGGGUGAACUCUUCGGCAuu UGCCGAAGAGUUCACCCUC -2.1 -2.4 -0.3 0 0 4 -42 44.8 -3.8 1 III 57.9 40.2 59.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0899 NM_004223 Huesken UBE2L6 9246 GGGUGAACUCUUCGGCAUUcu AAUGCCGAAGAGUUCACCC -0.9 -3.3 0.9 -1 -3 4 -39.5 43.4 1.5 2 III 52.6 29.2 51.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0900 NM_004223 Huesken UBE2L6 9246 CUUCGGCAUUCUUUCUGAAca UUCAGAAAGAAUGCCGAAG -0.9 -2.1 0.7 0 -1 4 -34.8 60.9 -2.8 2 III 42.1 32.8 57.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0901 NM_004223 Huesken UBE2L6 9246 AUUCUUUCUGAACAGCUCCgg GGAGCUGUUCAGAAAGAAU -3.3 -1.1 -0.3 3 4 2 -35.8 81.5 12.1 7 Ia 42.1 76 107.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0902 NM_004223 Huesken UBE2L6 9246 AACAGCUCCGGAUUCUGUGuc CACAGAAUCCGGAGCUGUU -2.1 -0.9 -1.2 3 4 4 -39.5 70.4 2.3 4 Ib 52.6 61.2 97.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0903 NM_004223 Huesken UBE2L6 9246 ACAGCUCCGGAUUCUGUGUca ACACAGAAUCCGGAGCUGU -2.2 -2.2 -1.1 2 1 4 -40.8 63 1.4 3 II 52.6 47.5 85.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0904 NM_004223 Huesken UBE2L6 9246 AGCUCCGGAUUCUGUGUCAgc UGACACAGAAUCCGGAGCU -2.1 -2.1 2.6 0 -1 4 -41 55.2 -6.1 5 II 52.6 37.8 54.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0905 NM_004223 Huesken UBE2L6 9246 GCUCCGGAUUCUGUGUCAGca CUGACACAGAAUCCGGAGC -2.1 -3.4 0.4 1 2 4 -41 45.8 3 1 II 57.9 32.6 79.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0906 NM_004223 Huesken UBE2L6 9246 GUCAGCAGGUCAGCGAGGUcc ACCUCGCUGACCUGCUGAC -2.2 -2.2 -1.5 1 0 3 -44.3 34.5 -6.3 1 III 63.2 34.8 58.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0907 NM_004223 Huesken UBE2L6 9246 GCAGGUCAGCGAGGUCCAUcc AUGGACCUCGCUGACCUGC -1.1 -3.4 -0.3 0 -1 3 -44.4 19.9 -4 0 III 63.2 19.9 43.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0908 NM_004223 Huesken UBE2L6 9246 AGGUCAGCGAGGUCCAUCCgc GGAUGGACCUCGCUGACCU -3.3 -2.1 0 2 2 3 -44.6 59.9 7.4 5 II 63.2 58.7 80.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0909 NM_004223 Huesken UBE2L6 9246 GGUCAGCGAGGUCCAUCCGca CGGAUGGACCUCGCUGACC -2.4 -3.3 -0.3 1 2 3 -44.9 37.6 8.1 1 II 68.4 36 71.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0910 NM_004223 Huesken UBE2L6 9246 AGCGAGGUCCAUCCGCAGGgg CCUGCGGAUGGACCUCGCU -3.3 -2.1 -3.1 2 2 4 -45.8 45 10.4 2 II 68.4 50.4 81.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0911 NM_004223 Huesken UBE2L6 9246 GCGAGGUCCAUCCGCAGGGgc CCCUGCGGAUGGACCUCGC -3.3 -3.4 -1.9 1 1 4 -47 31.1 0.1 1 II 73.7 42.4 59.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0912 NM_004223 Huesken UBE2L6 9246 GGUCCAUCCGCAGGGGCUCcc GAGCCCCUGCGGAUGGACC -2.4 -3.3 -0.8 2 1 5 -47.9 27.8 5.1 1 II 73.7 33.9 55.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0913 NM_004223 Huesken UBE2L6 9246 CCAUCCGCAGGGGCUCCCUga AGGGAGCCCCUGCGGAUGG -2.1 -3.3 -3.2 -1 -1 5 -48.7 33.8 -6 1 III 73.7 34.7 60.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0914 NM_004223 Huesken UBE2L6 9246 GGGGCUCCCUGAUAUUCGGuc CCGAAUAUCAGGGAGCCCC -3.3 -3.3 -1.6 1 1 5 -43.5 46.6 0 -2 II 63.2 37 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0915 NM_004223 Huesken UBE2L6 9246 UGAUAUUCGGUCUAUUCACca GUGAAUAGACCGAAUAUCA -2.2 -2.1 1.5 2 3 3 -33.7 82.1 7.8 7 Ia 36.8 70.7 89.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0916 NM_004223 Huesken UBE2L6 9246 CGGUCUAUUCACCAGCACAuu UGUGCUGGUGAAUAGACCG -2.1 -2.4 -2.5 -1 -4 3 -39.7 58.4 -3.4 1 III 52.6 40.7 59 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0917 NM_004223 Huesken UBE2L6 9246 CUAUUCACCAGCACAUUGAgg UCAAUGUGCUGGUGAAUAG -2.4 -2.1 1.2 0 -2 2 -35.9 71.5 -10.7 7 II 42.1 51 69.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0918 NM_004223 Huesken UBE2L6 9246 GCACAUUGAGGGCCUCCAGga CUGGAGGCCCUCAAUGUGC -2.1 -3.4 -0.5 2 1 5 -43.7 42.1 5.1 2 II 63.2 37.4 48.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0919 NM_004223 Huesken UBE2L6 9246 ACAUUGAGGGCCUCCAGGAcu UCCUGGAGGCCCUCAAUGU -2.4 -2.2 -0.5 2 1 5 -43.9 47.3 -8.5 5 II 57.9 47.7 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0920 NM_004223 Huesken UBE2L6 9246 CCUCCAGGACUUGGCAAGUcu ACUUGCCAAGUCCUGGAGG -2.2 -3.3 -1.6 -1 -2 3 -42.3 34.4 -3 0 III 57.9 29.9 31.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0921 NM_004223 Huesken UBE2L6 9246 UGGCAAGUCUUGGUGCAAGgc CUUGCACCAAGACUUGCCA -2.1 -2.1 -0.9 2 2 3 -39.7 51.9 5 5 II 52.6 54 89.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0922 NM_004223 Huesken UBE2L6 9246 UCUUGGUGCAAGGCUUCCAgu UGGAAGCCUUGCACCAAGA -2.1 -2.4 -0.8 2 1 3 -41.1 62.2 -1.5 7 II 52.6 57 77.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0923 NM_004223 Huesken UBE2L6 9246 UGGUGCAAGGCUUCCAGUUcu AACUGGAAGCCUUGCACCA -0.9 -2.1 0.4 1 0 3 -40.9 61.6 -3.3 5 II 52.6 54.6 77.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0924 NM_004223 Huesken UBE2L6 9246 CUUCCAGUUCUCACUGCUGau CAGCAGUGAGAACUGGAAG -2.1 -2.1 -3.7 0 1 2 -39 53.8 -6.9 2 II 52.6 50.3 74.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0925 NM_004223 Huesken UBE2L6 9246 UCCAGUUCUCACUGCUGAUga AUCAGCAGUGAGAACUGGA -1.1 -2.4 -3.7 0 0 2 -39.5 66.3 -4 4 II 47.4 49.8 82.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0926 NM_004223 Huesken UBE2L6 9246 CCAGUUCUCACUGCUGAUGau CAUCAGCAGUGAGAACUGG -2.1 -3.3 -3.7 0 -1 2 -39.2 57.6 -1.3 2 II 52.6 46.3 65.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0927 NM_004223 Huesken UBE2L6 9246 CAGUUCUCACUGCUGAUGAug UCAUCAGCAGUGAGAACUG -2.4 -2.1 -2.4 0 -2 2 -38.3 70.2 -1 4 II 47.4 44.8 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0928 NM_004223 Huesken UBE2L6 9246 UCUCACUGCUGAUGAUGGGca CCCAUCAUCAGCAGUGAGA -3.3 -2.4 -1.1 2 4 3 -40.8 58 2.7 5 Ib 52.6 55.8 74 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0929 NM_004223 Huesken UBE2L6 9246 GAUGAUGGGCAGGCAAAUCug GAUUUGCCUGCCCAUCAUC -2.4 -2.4 1.2 1 1 4 -39.5 48.6 12.4 4 II 52.6 46.9 71.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0930 NM_004223 Huesken UBE2L6 9246 CUCGUCCACGUUGGGGUGGua CCACCCCAACGUGGACGAG -3.3 -2.1 -4.2 -1 0 4 -44.2 38.9 1 1 II 68.4 41.6 67.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0931 NM_004223 Huesken UBE2L6 9246 UCGUCCACGUUGGGGUGGUag ACCACCCCAACGUGGACGA -2.2 -2.4 -4.7 0 1 4 -44.3 42.6 -4 3 II 63.2 44.4 64.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0932 NM_004223 Huesken UBE2L6 9246 CGUCCACGUUGGGGUGGUAga UACCACCCCAACGUGGACG -1.3 -2.4 -4.7 -1 -3 4 -43.2 25.8 -5.8 -1 III 63.2 13.8 37.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0933 NM_004223 Huesken UBE2L6 9246 UCCACGUUGGGGUGGUAGAuc UCUACCACCCCAACGUGGA -2.4 -2.4 -4.7 1 -1 4 -43.1 56 -3.8 3 II 57.9 45.8 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0934 NM_004223 Huesken UBE2L6 9246 UGGGGUGGUAGAUCUUGGUug ACCAAGAUCUACCACCCCA -2.2 -2.1 0 1 4 -41.7 58.1 -4 5 II 52.6 55.9 90.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0935 NM_004223 Huesken UBE2L6 9246 GGGGUGGUAGAUCUUGGUUgu AACCAAGAUCUACCACCCC -0.9 -3.3 0 -1 4 -40.5 54.2 6.1 2 III 52.6 33.3 43.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0936 NM_004223 Huesken UBE2L6 9246 GUGGUAGAUCUUGGUUGUGaa CACAACCAAGAUCUACCAC -2.1 -2.2 -1 1 2 -37 47.6 3 3 II 47.4 41.2 45.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0937 NM_004223 Huesken UBE2L6 9246 GUAGAUCUUGGUUGUGAAUuu AUUCACAACCAAGAUCUAC -1.1 -2.2 1.4 -1 -1 2 -33.8 66.6 1.8 3 II 36.8 37 51 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0938 NM_004223 Huesken UBE2L6 9246 GAUCUUGGUUGUGAAUUUGau CAAAUUCACAACCAAGAUC -2.1 -2.4 1.4 1 1 2 -32.1 70.4 3 5 II 36.8 48.2 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0939 NM_004223 Huesken UBE2L6 9246 UUGUGAAUUUGAUCAUGGGag CCCAUGAUCAAAUUCACAA -3.3 -0.9 -0.5 0 4 3 -33.4 78.4 0 6 Ia 36.8 68.6 95.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0940 NM_004223 Huesken UBE2L6 9246 UUGAUCAUGGGAGGCUUGAac UCAAGCCUCCCAUGAUCAA -2.4 -0.9 1.5 0 0 3 -39.5 62.5 -3.8 8 II 47.4 58 86.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0941 NM_004223 Huesken UBE2L6 9246 UGAUCAUGGGAGGCUUGAAcg UUCAAGCCUCCCAUGAUCA -0.9 -2.1 1.3 2 0 3 -39.5 60 -1.5 6 II 47.4 44.7 71.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0942 NM_004223 Huesken UBE2L6 9246 GGAGGCUUGAACGGAUACUcc AGUAUCCGUUCAAGCCUCC -2.1 -3.3 1.4 1 -1 3 -39.9 44.8 -4 3 III 52.6 37.9 53.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0943 NM_004223 Huesken UBE2L6 9246 AGGCUUGAACGGAUACUCCgg GGAGUAUCCGUUCAAGCCU -3.3 -2.1 -1.5 2 3 3 -39.9 60 7.1 4 II 52.6 59.9 84.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0944 NM_004223 Huesken UBE2L6 9246 ACGGAUACUCCGGCGGGAAgc UUCCCGCCGGAGUAUCCGU -0.9 -2.2 -3.1 1 -1 8 -44.1 32.3 -3.4 2 II 63.2 34.7 43 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0945 NM_004223 Huesken UBE2L6 9246 CGGAUACUCCGGCGGGAAGcu CUUCCCGCCGGAGUAUCCG -2.1 -2.4 -2.5 -1 -2 8 -44 37.1 0.4 0 II 68.4 28.2 38.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0946 NM_004223 Huesken UBE2L6 9246 ACUCCGGCGGGAAGCUGAUgc AUCAGCUUCCCGCCGGAGU -1.1 -2.2 -2.5 2 1 8 -44.6 31.1 -6.6 2 II 63.2 34.7 52.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0947 NM_004223 Huesken UBE2L6 9246 GGGAAGCUGAUGCGCAGGUug ACCUGCGCAUCAGCUUCCC -2.2 -3.3 -1.4 0 -1 4 -44.1 32.1 1.1 1 III 63.2 30.6 70.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0948 NM_004223 Huesken UBE2L6 9246 GGAAGCUGAUGCGCAGGUUga AACCUGCGCAUCAGCUUCC -0.9 -3.3 -1.4 1 -1 4 -41.7 39.5 -6.3 1 III 57.9 29.6 51.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0949 NM_004223 Huesken UBE2L6 9246 UGCGCAGGUUGAAGGCUUUca AAAGCCUUCAACCUGCGCA -0.9 -2.1 0.3 -1 -1 4 -40 45.1 -6.6 5 II 52.6 43.9 69.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0950 NM_004223 Huesken UBE2L6 9246 GUAGGGAGGUUGGUCGGGUag ACCCGACCAACCUCCCUAC -2.2 -2.2 1.7 1 2 4 -44.3 29.9 -1.6 2 III 63.2 39.9 64 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0951 NM_004223 Huesken UBE2L6 9246 GGGAGGUUGGUCGGGUAGGag CCUACCCGACCAACCUCCC -3.3 -3.3 1.7 1 0 4 -45.4 30.3 -2.4 1 II 68.4 37.8 55.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0952 NM_004223 Huesken UBE2L6 9246 GAGGUUGGUCGGGUAGGAGga CUCCUACCCGACCAACCUC -2.1 -2.4 2 0 2 4 -43.3 41.1 2.3 2 II 63.2 38.3 63.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0953 NM_004223 Huesken UBE2L6 9246 GGUUGGUCGGGUAGGAGGAga UCCUCCUACCCGACCAACC -2.4 -3.3 2 1 -1 4 -44.5 38.2 -3.3 2 III 63.2 28.1 49.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0954 NM_004223 Huesken UBE2L6 9246 UUGGUCGGGUAGGAGGAGAgc UCUCCUCCUACCCGACCAA -2.4 -0.9 2 1 0 4 -43.5 46.1 -1.5 5 II 57.9 52.4 79.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0955 NM_004223 Huesken UBE2L6 9246 GUCGGGUAGGAGGAGAGCGug CGCUCUCCUCCUACCCGAC -2.4 -2.2 2 2 2 4 -45.1 33 2.3 1 II 68.4 47.7 73.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0956 NM_004223 Huesken UBE2L6 9246 GGUAGGAGGAGAGCGUGCCac GGCACGCUCUCCUCCUACC -3.3 -3.3 0.6 1 2 3 -45.8 37 7.4 3 II 68.4 44.9 62.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0957 NM_004223 Huesken UBE2L6 9246 UAGGAGGAGAGCGUGCCACac GUGGCACGCUCUCCUCCUA -2.2 -1.3 0.6 1 4 3 -44.6 47.5 10.1 6 II 63.2 64.3 96.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0958 NM_004223 Huesken UBE2L6 9246 AGGAGAGCGUGCCACACCAgg UGGUGUGGCACGCUCUCCU -2.1 -2.1 -2.1 2 0 3 -45.2 35.9 -3.7 2 II 63.2 42.9 89.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0959 NM_004223 Huesken UBE2L6 9246 GAGCGUGCCACACCAGGACau GUCCUGGUGUGGCACGCUC -2.2 -2.4 -2.1 2 1 3 -45.3 36.6 7.5 1 II 68.4 41.7 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0960 NM_004223 Huesken UBE2L6 9246 CAGGACAUUGGCAUCAUCGcu CGAUGAUGCCAAUGUCCUG -2.4 -2.1 0.1 -1 1 3 -38.6 61.8 -1.9 4 II 52.6 60.6 97.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0961 NM_004223 Huesken UBE2L6 9246 AGGACAUUGGCAUCAUCGCug GCGAUGAUGCCAAUGUCCU -3.4 -2.1 0.1 3 3 3 -39.9 61.2 5.1 4 Ib 52.6 57.3 107.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0962 NM_004223 Huesken UBE2L6 9246 GGACAUUGGCAUCAUCGCUgg AGCGAUGAUGCCAAUGUCC -2.1 -3.3 -0.1 3 0 3 -39.9 52.3 6.5 3 II 52.6 40.8 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0963 NM_004223 Huesken UBE2L6 9246 GGCAUCAUCGCUGGACAGGuu CCUGUCCAGCGAUGAUGCC -3.3 -3.3 -0.1 0 0 3 -43.3 43.4 0.7 2 II 63.2 37.8 77.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0964 NM_004223 Huesken UBE2L6 9246 CGCUGGACAGGUUCCGCAGgu CUGCGGAACCUGUCCAGCG -2.1 -2.4 -2.4 -1 -1 4 -44.2 45.4 1 0 II 68.4 37.3 76.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0965 NM_004223 Huesken UBE2L6 9246 CUGGACAGGUUCCGCAGGUau ACCUGCGGAACCUGUCCAG -2.2 -2.1 -2.4 -1 -1 4 -43.9 31.7 -3.2 1 III 63.2 38.7 73.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0966 NM_004223 Huesken UBE2L6 9246 ACAGGUUCCGCAGGUAUGGgg CCAUACCUGCGGAACCUGU -3.3 -2.2 -0.3 2 3 4 -41.8 44.6 -2.4 4 Ib 57.9 55.9 88.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0967 NM_016406 Huesken Ufc1 51506 AUUUCUCUUUGUGUUGGAUga AUCCAACACAAAGAGAAAU -1.1 -1.1 2.4 1 3 2 -32.1 88.6 1.4 5 II 31.6 48.7 69.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0968 NM_016406 Huesken Ufc1 51506 UUCUCUUUGUGUUGGAUGAcg UCAUCCAACACAAAGAGAA -2.4 -0.9 2.4 1 0 2 -34.6 91.1 -0.7 7 II 36.8 58.8 93 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0969 NM_016406 Huesken Ufc1 51506 CUCUUUGUGUUGGAUGACGcc CGUCAUCCAACACAAAGAG -2.4 -2.1 1 0 0 2 -35.9 62.9 -2 4 II 47.4 54.2 86.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0970 NM_016406 Huesken Ufc1 51506 UUGUGUUGGAUGACGCCCUuc AGGGCGUCAUCCAACACAA -2.1 -0.9 -3.4 2 2 5 -40.5 65.1 -6.6 6 II 52.6 71.8 107.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0971 NM_016406 Huesken Ufc1 51506 CCCUUCUGAAUCAGAUCAGgg CUGAUCUGAUUCAGAAGGG -2.1 -3.3 -3.4 -1 -1 3 -37.3 56.3 -6.9 3 II 47.4 40.7 73.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0972 NM_016406 Huesken Ufc1 51506 UGAAUCAGAUCAGGGAUUUcc AAAUCCCUGAUCUGAUUCA -0.9 -2.1 0.2 -1 0 3 -35.1 64.7 -6.3 8 II 36.8 55.2 81 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0973 NM_016406 Huesken Ufc1 51506 UCAGGGAUUUCCACUGCCAgc UGGCAGUGGAAAUCCCUGA -2.1 -2.4 -0.6 0 1 3 -41.5 48 -11 5 II 52.6 56.7 71.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0974 NM_016406 Huesken Ufc1 51506 AGGGAUUUCCACUGCCAGCca GCUGGCAGUGGAAAUCCCU -3.4 -2.1 -0.6 2 2 3 -42.5 57.9 10.1 3 Ib 57.9 58.4 48.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0975 NM_016406 Huesken Ufc1 51506 ACUGCCAGCCAUGGACCCAgc UGGGUCCAUGGCUGGCAGU -2.1 -2.2 -1.3 1 1 3 -45.9 38.8 1.6 2 II 63.2 40.1 35.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0976 NM_016406 Huesken Ufc1 51506 CUGCCAGCCAUGGACCCAGcc CUGGGUCCAUGGCUGGCAG -2.1 -2.1 -1.3 1 0 3 -45.8 33.3 -2 1 II 68.4 45.7 60.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0977 NM_016406 Huesken Ufc1 51506 UGGACCCAGCCCCAGAGCCau GGCUCUGGGGCUGGGUCCA -3.3 -2.1 -4.6 1 3 5 -49.5 44.1 5.1 2 II 73.7 58 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0978 NM_016406 Huesken Ufc1 51506 AGCCCCAGAGCCAUGAGAUga AUCUCAUGGCUCUGGGGCU -1.1 -2.1 -3.4 2 1 5 -44.1 47.6 -8.9 1 II 57.9 39.7 53.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0979 NM_016406 Huesken Ufc1 51506 AGCCAUGAGAUGAGCUAGUcc ACUAGCUCAUCUCAUGGCU -2.2 -2.1 -1.7 2 0 3 -39.8 47 -3.9 4 II 47.4 47.1 53.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0980 NM_016406 Huesken Ufc1 51506 CCAUGAGAUGAGCUAGUCCaa GGACUAGCUCAUCUCAUGG -3.3 -3.3 1.3 -1 1 2 -40 53.7 12.4 4 II 52.6 49.2 61.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0981 NM_016406 Huesken Ufc1 51506 UCCAAAUUUGGGCACAUUCcu GAAUGUGCCCAAAUUUGGA -2.4 -2.4 -1.5 1 1 4 -35.4 74.7 12.5 6 Ia 42.1 67 67.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0982 NM_016406 Huesken Ufc1 51506 AUUUGGGCACAUUCCUGGCcc GCCAGGAAUGUGCCCAAAU -3.4 -1.1 -0.8 1 5 4 -40 70.9 12.7 6 Ib 52.6 63 77.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0983 NM_016406 Huesken Ufc1 51506 AUUCCUGGCCCACAAAGGUuu ACCUUUGUGGGCCAGGAAU -2.2 -1.1 -1.5 3 3 5 -41 53 -3.9 4 II 52.6 53.9 56.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0984 NM_016406 Huesken Ufc1 51506 ACAAAGGUUUGAAAUGAUCcg GAUCAUUUCAAACCUUUGU -2.4 -2.2 0.4 1 2 2 -30.9 66 7.5 6 Ib 31.6 61.1 98.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0985 NM_016406 Huesken Ufc1 51506 AAGGUUUGAAAUGAUCCGUca ACGGAUCAUUUCAAACCUU -2.2 -0.9 -0.3 2 2 3 -33.6 76 1.4 6 II 36.8 63.2 106 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0986 NM_016406 Huesken Ufc1 51506 AGGUUUGAAAUGAUCCGUCag GACGGAUCAUUUCAAACCU -2.4 -2.1 -0.3 1 3 3 -35.1 71.1 7.1 6 Ib 42.1 63.9 122.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0987 NM_016406 Huesken Ufc1 51506 GUUUGAAAUGAUCCGUCAGgc CUGACGGAUCAUUUCAAAC -2.1 -2.2 -0.3 0 2 3 -33.9 69.9 7.7 4 II 42.1 47.1 65.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0988 NM_016406 Huesken Ufc1 51506 UUGAAAUGAUCCGUCAGGCau GCCUGACGGAUCAUUUCAA -3.4 -0.9 -0.4 1 5 3 -37.5 67.8 7.7 7 Ia 47.4 71.4 117.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0989 NM_016406 Huesken Ufc1 51506 CCGUCAGGCAUAUUUUGCCac GGCAAAAUAUGCCUGACGG -3.3 -3.3 -4.7 0 1 3 -38.3 60.9 7.7 2 II 52.6 50.3 99.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0990 NM_016406 Huesken Ufc1 51506 UGCCACCCCUGUACAUCUUug AAGAUGUACAGGGGUGGCA -0.9 -2.1 0.5 2 0 4 -41.5 56.3 -0.8 4 II 52.6 45.4 62.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0991 NM_016406 Huesken Ufc1 51506 CACCCCUGUACAUCUUUGCug GCAAAGAUGUACAGGGGUG -3.4 -2.1 0.5 1 0 4 -39.1 68.9 3.1 4 II 52.6 53.3 108.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0992 NM_016406 Huesken Ufc1 51506 CCUGUACAUCUUUGCUGUCuu GACAGCAAAGAUGUACAGG -2.4 -3.3 -0.1 -2 0 2 -37 54.4 8.4 2 II 47.4 39.6 50.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0993 NM_016406 Huesken Ufc1 51506 UGUACAUCUUUGCUGUCUUuc AAGACAGCAAAGAUGUACA -0.9 -2.1 -0.1 1 2 2 -34.6 81.3 0.8 6 II 36.8 58.5 112.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0994 NM_016406 Huesken Ufc1 51506 AUCUUUGCUGUCUUUCCAUcc AUGGAAAGACAGCAAAGAU -1.1 -1.1 0.3 1 2 2 -34.5 81.4 -4 6 II 36.8 57.4 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0995 NM_016406 Huesken Ufc1 51506 CUUUGCUGUCUUUCCAUCCag GGAUGGAAAGACAGCAAAG -3.3 -2.1 0.3 0 1 2 -36.7 79.3 8.4 5 II 47.4 63.4 102.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0996 NM_016406 Huesken Ufc1 51506 UCUUUCCAUCCAGCUCAGGaa CCUGAGCUGGAUGGAAAGA -3.3 -2.4 -1 0 3 2 -40.5 60.5 -2.4 5 Ib 52.6 57.6 120.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0997 NM_016406 Huesken Ufc1 51506 CAUCCAGCUCAGGAACUGCaa GCAGUUCCUGAGCUGGAUG -3.4 -2.1 -4.4 0 1 2 -41.6 47.5 7.7 2 II 57.9 48.2 80.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0998 NM_016406 Huesken Ufc1 51506 CCAGCUCAGGAACUGCAAUuu AUUGCAGUUCCUGAGCUGG -1.1 -3.3 -4.4 0 -2 2 -40.1 47.1 1.1 0 III 52.6 32.5 61.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si0999 NM_016406 Huesken Ufc1 51506 GAACUGCAAUUUCUGGGGCag GCCCCAGAAAUUGCAGUUC -3.4 -2.4 0.6 1 4 5 -38.9 56.4 15.2 3 II 52.6 46.8 61.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1000 NM_016406 Huesken Ufc1 51506 AACUGCAAUUUCUGGGGCAgu UGCCCCAGAAAUUGCAGUU -2.1 -0.9 -0.1 0 1 5 -38.6 56.7 -6.1 5 II 47.4 47.2 44.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1001 NM_016406 Huesken Ufc1 51506 UGCAAUUUCUGGGGCAGUAgu UACUGCCCCAGAAAUUGCA -1.3 -2.1 -0.1 1 -1 5 -39 60.2 -1.1 6 II 47.4 48.1 52.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1002 NM_016406 Huesken Ufc1 51506 UGGGGCAGUAGUAGGAUAUgu AUAUCCUACUACUGCCCCA -1.1 -2.1 3.5 -1 -1 5 -40 58.8 -3.5 6 II 47.4 51.6 78.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1003 NM_016406 Huesken Ufc1 51506 CAGUAGUAGGAUAUGUGAUag AUCACAUAUCCUACUACUG -1.1 -2.1 3.5 1 -1 2 -34.5 71 1.8 4 II 36.8 44.3 69.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1004 NM_016406 Huesken Ufc1 51506 AUAUGUGAUAGGAAUGUCAaa UGACAUUCCUAUCACAUAU -2.1 -1.1 1 1 1 2 -33.3 75.7 -6.3 8 II 31.6 63.7 114.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1005 NM_016406 Huesken Ufc1 51506 GAUAGGAAUGUCAAACUCGau CGAGUUUGACAUUCCUAUC -2.4 -2.4 0 0 2 2 -34.3 58.2 -4.9 5 II 42.1 60.5 95.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1006 NM_016406 Huesken Ufc1 51506 UCAAACUCGAUGUCAAACUca AGUUUGACAUCGAGUUUGA -2.1 -2.4 0.8 2 1 2 -33.8 77.2 -1.3 8 II 36.8 69.7 121.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1007 NM_016406 Huesken Ufc1 51506 GAUGUCAAACUCAUAUUUCag GAAAUAUGAGUUUGACAUC -2.4 -2.4 1.3 0 2 1 -30.6 77.6 4.8 5 II 31.6 56.4 66.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1008 NM_016406 Huesken Ufc1 51506 AUGUCAAACUCAUAUUUCAgg UGAAAUAUGAGUUUGACAU -2.1 -1.1 1.3 2 0 1 -30.3 82.2 -6.1 6 II 26.3 57.2 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1009 NM_016406 Huesken Ufc1 51506 AACUCAUAUUUCAGGAGGUca ACCUCCUGAAAUAUGAGUU -2.2 -0.9 0.2 1 2 2 -34.9 66.1 -8.9 5 II 36.8 51.8 43.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1010 NM_016406 Huesken Ufc1 51506 CAGGAGGUCAUGGAUAUACca GUAUAUCCAUGACCUCCUG -2.2 -2.1 2.7 0 -1 2 -37.9 54.2 8.1 5 II 47.4 53.5 96 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1011 NM_016406 Huesken Ufc1 51506 GGAGGUCAUGGAUAUACCAgc UGGUAUAUCCAUGACCUCC -2.1 -3.3 -1.4 0 -1 2 -39.1 47 -3.8 0 III 47.4 37.2 31.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1012 NM_016406 Huesken Ufc1 51506 AUAUACCAGCAUUUUCCAAac UUGGAAAAUGCUGGUAUAU -0.9 -1.1 1.5 2 2 2 -32.5 80.6 6.6 6 II 31.6 48.6 56.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1013 NM_016406 Huesken Ufc1 51506 UUUCCAAACCACCGAGUUCcu GAACUCGGUGGUUUGGAAA -2.4 -0.9 -1.1 1 3 3 -36.9 67.6 9.8 6 Ia 47.4 65.4 97.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1014 NM_016406 Huesken Ufc1 51506 CCAAACCACCGAGUUCCUUcc AAGGAACUCGGUGGUUUGG -0.9 -3.3 -1.5 0 -1 3 -39 44.7 -0.9 2 III 52.6 34.5 32.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1015 NM_016406 Huesken Ufc1 51506 AACCACCGAGUUCCUUCCUug AGGAAGGAACUCGGUGGUU -2.1 -0.9 0.5 2 2 3 -40.5 56.7 4.2 4 II 52.6 49 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1016 NM_016406 Huesken Ufc1 51506 GUUCCUUCCUUGUUGGACUcc AGUCCAACAAGGAAGGAAC -2.1 -2.2 -2.1 3 1 2 -37.8 73.8 -1.6 2 II 47.4 50 83.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1017 NM_016406 Huesken Ufc1 51506 CUUCCUUGUUGGACUCCAGuc CUGGAGUCCAACAAGGAAG -2.1 -2.1 -2.1 1 1 2 -38.9 61.5 -4.6 2 II 52.6 48.3 66.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1018 NM_016406 Huesken Ufc1 51506 UGGACUCCAGUCGGAACCAau UGGUUCCGACUGGAGUCCA -2.1 -2.1 -2.8 -1 0 3 -43.2 44.5 -6.1 2 II 57.9 48.9 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1019 NM_016406 Huesken Ufc1 51506 UCGGAACCAAUCGUUGUCAgc UGACAACGAUUGGUUCCGA -2.1 -2.4 0.1 0 0 3 -37.7 55.5 -1.1 6 II 47.4 52.2 76.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1020 NM_016406 Huesken Ufc1 51506 GGAACCAAUCGUUGUCAGCau GCUGACAACGAUUGGUUCC -3.4 -3.3 0.1 -1 1 2 -38.4 60.1 10.4 3 II 52.6 43.6 78 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1021 NM_016406 Huesken Ufc1 51506 CGUUGUCAGCAUUCUUGUUgu AACAAGAAUGCUGACAACG -0.9 -2.4 1.7 0 -2 2 -34.5 69.2 -0.7 2 III 42.1 34.2 43.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1022 NM_016406 Huesken Ufc1 51506 UUGUCAGCAUUCUUGUUGUuc ACAACAAGAAUGCUGACAA -2.2 -0.9 1.7 0 2 2 -34.2 84.9 -4 7 II 36.8 63.1 86.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1023 NM_016406 Huesken Ufc1 51506 CAUUCUUGUUGUUCUCCACau GUGGAGAACAACAAGAAUG -2.2 -2.1 0.3 0 1 2 -34.4 86 8.4 4 II 42.1 52.4 68.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1024 NM_016406 Huesken Ufc1 51506 GUUGUUCUCCACAUACCGGau CCGGUAUGUGGAGAACAAC -3.3 -2.2 -0.7 1 4 4 -38.5 63.3 -0.3 3 II 52.6 52.9 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1025 NM_016406 Huesken Ufc1 51506 UCUCCACAUACCGGAUAAGgg CUUAUCCGGUAUGUGGAGA -2.1 -2.4 -2.4 0 2 4 -38 52.4 -4.7 4 II 47.4 48.3 78.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1026 NM_016406 Huesken Ufc1 51506 ACAUACCGGAUAAGGGACUga AGUCCCUUAUCCGGUAUGU -2.1 -2.2 -0.2 1 1 4 -39 47 -3.9 6 II 47.4 48.4 74.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1027 NM_016406 Huesken Ufc1 51506 CAUACCGGAUAAGGGACUGau CAGUCCCUUAUCCGGUAUG -2.1 -2.1 -0.2 -2 1 4 -38.9 50.4 0.3 4 II 52.6 43.9 78.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1028 NM_016406 Huesken Ufc1 51506 AUACCGGAUAAGGGACUGAua UCAGUCCCUUAUCCGGUAU -2.4 -1.1 -0.2 1 1 4 -39.2 48.2 -1.5 7 II 47.4 49.7 88.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1029 NM_016406 Huesken Ufc1 51506 UACCGGAUAAGGGACUGAUau AUCAGUCCCUUAUCCGGUA -1.1 -1.3 -0.2 1 1 4 -39.2 58.3 -4 6 II 47.4 55.5 99.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1030 NM_016406 Huesken Ufc1 51506 CUGAUAUUCCUCCUUCAGUcg ACUGAAGGAGGAAUAUCAG -2.2 -2.1 -0.9 1 -1 2 -36.3 72.8 -3.6 4 II 42.1 52 75.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1031 NM_016406 Huesken Ufc1 51506 AUAUUCCUCCUUCAGUCGCug GCGACUGAAGGAGGAAUAU -3.4 -1.1 0.9 2 5 3 -37.9 76 12.8 6 Ia 47.4 66.3 106.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1032 NM_016406 Huesken Ufc1 51506 UAUUCCUCCUUCAGUCGCUgc AGCGACUGAAGGAGGAAUA -2.1 -1.3 0.9 1 3 3 -38.9 72.5 -8.9 7 II 47.4 63.9 93.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1033 NM_016406 Huesken Ufc1 51506 AUUCCUCCUUCAGUCGCUGca CAGCGACUGAAGGAGGAAU -2.1 -1.1 0.4 2 5 3 -39.7 59.7 0 4 Ib 52.6 57 100.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1034 NM_016406 Huesken Ufc1 51506 UCCUUCAGUCGCUGCACCCac GGGUGCAGCGACUGAAGGA -3.3 -2.4 -0.2 -1 3 3 -44.2 59.4 5.1 5 Ib 63.2 62.9 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1035 NM_016406 Huesken Ufc1 51506 AGUCGCUGCACCCACAACUca AGUUGUGGGUGCAGCGACU -2.1 -2.1 -4.7 4 1 3 -42.6 53.7 -6.3 3 II 57.9 55.3 80.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1036 NM_016406 Huesken Ufc1 51506 UCACGAUCUCGGGGUCCGGcg CCGGACCCCGAGAUCGUGA -3.3 -2.4 -1.4 1 4 5 -45.4 35 0 3 Ib 68.4 53.9 56.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1037 NM_014176 Huesken HSPC150 29089 UUUCUUUUCUAUGCCUACUag AGUAGGCAUAGAAAAGAAA -2.1 -0.9 2.7 3 2 3 -32.4 96.4 1.4 7 II 31.6 73.6 101.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1038 NM_014176 Huesken HSPC150 29089 CUUUUCUAUGCCUACUAGCug GCUAGUAGGCAUAGAAAAG -3.4 -2.1 -2.1 0 1 3 -35 80.2 0.7 4 II 42.1 62 106 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1039 NM_014176 Huesken HSPC150 29089 UACUAGCUGACUGGCCUUCcu GAAGGCCAGUCAGCUAGUA -2.4 -1.3 -1.6 0 2 4 -40.8 63 10.8 7 Ib 52.6 62.4 91.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1040 NM_014176 Huesken HSPC150 29089 CCUUCCUUUUCUGUGUUGAgu UCAACACAGAAAAGGAAGG -2.4 -3.3 1.2 0 -2 2 -35.3 75.7 -2.8 4 III 42.1 36.1 65.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1041 NM_014176 Huesken HSPC150 29089 UGUUGAGUUGUGUACUCUGga CAGAGUACACAACUCAACA -2.1 -2.1 -3.5 0 3 1 -35.7 70.7 0 5 Ib 42.1 65.5 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1042 NM_014176 Huesken HSPC150 29089 UUGUGUACUCUGGAGUCACca GUGACUCCAGAGUACACAA -2.2 -0.9 -0.5 0 3 2 -38.4 66.4 7.4 6 Ia 47.4 69.3 108 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1043 NM_014176 Huesken HSPC150 29089 GUGUACUCUGGAGUCACCAgc UGGUGACUCCAGAGUACAC -2.1 -2.2 -1.6 1 0 2 -40.8 55.9 1.3 3 II 52.6 45.1 80.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1044 NM_014176 Huesken HSPC150 29089 GUCACCAGCCUCUGGUAGAuu UCUACCAGAGGCUGGUGAC -2.4 -2.2 -5.4 0 -2 3 -43.1 49.1 -6.1 1 III 57.9 33.6 63.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1045 NM_014176 Huesken HSPC150 29089 UCACCAGCCUCUGGUAGAUua AUCUACCAGAGGCUGGUGA -1.1 -2.4 -5.4 1 1 3 -42 46.3 -3.3 4 II 52.6 41.7 97 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1046 NM_014176 Huesken HSPC150 29089 CUCUGGUAGAUUAUCAAGCau GCUUGAUAAUCUACCAGAG -3.4 -2.1 0.9 1 1 2 -35.3 73 8.2 4 II 42.1 63.1 101 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1047 NM_014176 Huesken HSPC150 29089 AGAUUAUCAAGCAUCUCUUcc AAGAGAUGCUUGAUAAUCU -0.9 -2.1 -1.3 2 2 2 -32.9 82.6 -6.6 6 II 31.6 58.8 99.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1048 NM_014176 Huesken HSPC150 29089 GAUUAUCAAGCAUCUCUUCcu GAAGAGAUGCUUGAUAAUC -2.4 -2.4 0.5 0 1 2 -33.2 76.1 7.8 5 II 36.8 50.6 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1049 NM_014176 Huesken HSPC150 29089 UUAUCAAGCAUCUCUUCCUca AGGAAGAGAUGCUUGAUAA -2.1 -0.9 0.7 1 3 2 -35.1 85.3 -6.3 8 II 36.8 74.5 113 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1050 NM_014176 Huesken HSPC150 29089 AUCAAGCAUCUCUUCCUCAuc UGAGGAAGAGAUGCUUGAU -2.1 -1.1 0.7 1 1 2 -37.4 67.3 -1.1 6 II 42.1 55.9 91.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1051 NM_014176 Huesken HSPC150 29089 CAAGCAUCUCUUCCUCAUCag GAUGAGGAAGAGAUGCUUG -2.4 -2.1 0.7 0 0 2 -37.4 65.4 10.8 3 II 47.4 54.8 95.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1052 NM_014176 Huesken HSPC150 29089 GCAUCUCUUCCUCAUCAGCcu GCUGAUGAGGAAGAGAUGC -3.4 -3.4 0.8 0 1 2 -39.9 62 10.5 2 II 52.6 43.6 73.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1053 NM_014176 Huesken HSPC150 29089 UUUCUGUCUUGCAUGCUUCuc GAAGCAUGCAAGACAGAAA -2.4 -0.9 1.8 2 4 2 -35.6 84.1 4.8 8 Ia 42.1 75.9 97.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1054 NM_014176 Huesken HSPC150 29089 CUGUCCACUGUCUGGCAUUcu AAUGCCAGACAGUGGACAG -0.9 -2.1 -1.3 -2 -3 3 -40.2 55.7 -8.3 2 III 52.6 42.6 77.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1055 NM_014176 Huesken HSPC150 29089 GUCCACUGUCUGGCAUUCUug AGAAUGCCAGACAGUGGAC -2.1 -2.2 -1.3 2 -1 3 -40.5 49.8 -1.3 3 III 52.6 41.1 95 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1056 NM_014176 Huesken HSPC150 29089 UCUGGCAUUCUUGAGGAAGgc CUUCCUCAAGAAUGCCAGA -2.1 -2.4 1.1 0 2 3 -38.1 60.9 3 5 II 47.4 59.7 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1057 NM_014176 Huesken HSPC150 29089 AUUAUAUUUAAAUUCUGAGga CUCAGAAUUUAAAUAUAAU -2.1 -1.1 2.8 2 5 1 -24.8 108.8 4.6 8 Ia 15.8 73.1 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1058 NM_014176 Huesken HSPC150 29089 UUAAAUUCUGAGGAUAUGUca ACAUAUCCUCAGAAUUUAA -2.2 -0.9 1.6 1 2 2 -30.6 89.1 1 9 II 26.3 76.3 114 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1059 NM_014176 Huesken HSPC150 29089 AGCCAUGAGCGGGUCAUCAgg UGAUGACCCGCUCAUGGCU -2.1 -2.1 -1.1 3 0 5 -43.3 45.5 1.3 3 II 57.9 43.4 75.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1060 NM_014176 Huesken HSPC150 29089 CCAUGAGCGGGUCAUCAGGgu CCUGAUGACCCGCUCAUGG -3.3 -3.3 -0.8 0 0 5 -43.2 40.9 3.4 2 II 63.2 41.7 83.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1061 NM_014176 Huesken HSPC150 29089 CAUGAGCGGGUCAUCAGGGuu CCCUGAUGACCCGCUCAUG -3.3 -2.1 -0.8 0 3 5 -43.2 38.6 -1.9 2 II 63.2 50.2 91.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1062 NM_014176 Huesken HSPC150 29089 AUGAGCGGGUCAUCAGGGUug ACCCUGAUGACCCGCUCAU -2.2 -1.1 -0.1 2 2 5 -43.3 44.4 -6.3 4 II 57.9 47.7 100.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1063 NM_014176 Huesken HSPC150 29089 GGGUCAUCAGGGUUGGGUUcu AACCCAACCCUGAUGACCC -0.9 -3.3 1.6 1 -1 3 -42.5 55.9 -1.6 1 III 57.9 30.6 52.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1064 NM_014176 Huesken HSPC150 29089 UGGGUUCUGACAUGAGCAGcu CUGCUCAUGUCAGAACCCA -2.1 -2.1 0.1 0 2 3 -40.4 56.2 -2.4 5 II 52.6 54.8 104.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1065 NM_014176 Huesken HSPC150 29089 GGUUCUGACAUGAGCAGCUga AGCUGCUCAUGUCAGAACC -2.1 -3.3 -0.1 0 0 2 -40.5 52.3 -6.6 4 III 52.6 42 79.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1066 NM_014176 Huesken HSPC150 29089 GCAGCUGAAUAGAGGUCAAca UUGACCUCUAUUCAGCUGC -0.9 -3.4 0.6 -1 -2 2 -38.4 41.6 -4 2 III 47.4 23.4 49.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1067 NM_014176 Huesken HSPC150 29089 UAGAGGUCAACACAGUUGCga GCAACUGUGUUGACCUCUA -3.4 -1.3 -0.8 1 3 2 -38.1 72.7 7.5 8 Ib 47.4 75.9 114.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1068 NM_014176 Huesken HSPC150 29089 GGUCAACACAGUUGCGAUGuu CAUCGCAACUGUGUUGACC -2.1 -3.3 -0.8 1 0 3 -38.2 51.4 5.7 3 II 52.6 35.5 84.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1069 NM_014176 Huesken HSPC150 29089 AACACAGUUGCGAUGUUGAgg UCAACAUCGCAACUGUGUU -2.4 -0.9 -0.8 1 1 3 -35.8 68.5 -6.4 6 II 42.1 50.5 102.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1070 NM_014176 Huesken HSPC150 29089 ACAGUUGCGAUGUUGAGGGau CCCUCAACAUCGCAACUGU -3.3 -2.2 1.5 2 5 3 -39.3 62.1 2.3 6 Ib 52.6 63.6 106.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1071 NM_014176 Huesken HSPC150 29089 GGGAUGGUCUCCAAGCACCuu GGUGCUUGGAGACCAUCCC -3.3 -3.3 -2.3 1 0 3 -44 43.6 0.1 1 II 63.2 48.1 80.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1072 NM_014176 Huesken HSPC150 29089 GGAUGGUCUCCAAGCACCUuu AGGUGCUUGGAGACCAUCC -2.1 -3.3 -2.5 0 0 2 -42.8 37.7 -8.9 1 III 57.9 40.2 65.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1073 NM_014176 Huesken HSPC150 29089 GAUGGUCUCCAAGCACCUUuu AAGGUGCUUGGAGACCAUC -0.9 -2.4 -2.5 1 0 2 -40.4 46.5 -1.7 1 III 52.6 37.3 60.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1074 NM_014176 Huesken HSPC150 29089 GUCUCCAAGCACCUUUUGGug CCAAAAGGUGCUUGGAGAC -3.3 -2.2 -2 1 2 2 -38.7 70.3 4.7 3 II 52.6 47.1 84.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1075 NM_014176 Huesken HSPC150 29089 AGCACCUUUUGGUGGCAAUuu AUUGCCACCAAAAGGUGCU -1.1 -2.1 -4.2 1 -1 3 -38.4 65.8 -4 3 II 47.4 38.5 43.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1076 NM_014176 Huesken HSPC150 29089 CUUUUGGUGGCAAUUUGAGaa CUCAAAUUGCCACCAAAAG -2.1 -2.1 1.3 0 2 3 -33.7 68.2 -4.6 5 II 42.1 51 68.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1077 NM_014176 Huesken HSPC150 29089 UGGUGGCAAUUUGAGAACAuc UGUUCUCAAAUUGCCACCA -2.1 -2.1 1.7 0 -1 3 -36.5 57.3 -0.7 4 II 42.1 51 53.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1078 NM_014176 Huesken HSPC150 29089 GGCAAUUUGAGAACAUCCAga UGGAUGUUCUCAAAUUGCC -2.1 -3.3 1 2 -2 3 -35.7 61.8 -3.6 4 II 42.1 41.7 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1079 NM_014176 Huesken HSPC150 29089 CAAUUUGAGAACAUCCAGAca UCUGGAUGUUCUCAAAUUG -2.4 -2.1 0.9 0 -1 2 -33.5 72.4 -6.1 6 II 36.8 53.5 80.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1080 NM_014176 Huesken HSPC150 29089 GAGAACAUCCAGACAAAUCcu GAUUUGUCUGGAUGUUCUC -2.4 -2.4 1.4 1 0 2 -35.1 66.5 9.8 4 II 42.1 53.9 75 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1081 NM_014176 Huesken HSPC150 29089 AACAUCCAGACAAAUCCUUcc AAGGAUUUGUCUGGAUGUU -0.9 -0.9 0 2 1 2 -34.5 65.6 -8.9 6 II 36.8 54.9 79.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1082 NM_014176 Huesken HSPC150 29089 CAUCCAGACAAAUCCUUCCag GGAAGGAUUUGUCUGGAUG -3.3 -2.1 0 1 1 2 -37.1 71.1 7.7 5 II 47.4 59.6 96.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1083 NM_014176 Huesken HSPC150 29089 GACAAAUCCUUCCAGCAGAau UCUGCUGGAAGGAUUUGUC -2.4 -2.4 0.1 2 -2 2 -38.2 53.6 -1 4 II 47.4 38.8 87.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1084 NM_014176 Huesken HSPC150 29089 AAUCCUUCCAGCAGAAUCAau UGAUUCUGCUGGAAGGAUU -2.1 -0.9 -3 3 1 2 -37.1 72.3 -8.7 6 II 42.1 59.1 95.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1085 NM_014176 Huesken HSPC150 29089 AAUCAAUGUUUGGAUGAUAaa UAUCAUCCAAACAUUGAUU -1.3 -0.9 -0.1 3 0 2 -30.4 66.2 -1.1 6 II 26.3 50.3 67.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1086 NM_014176 Huesken HSPC150 29089 UGUUUGGAUGAUAAAUUGGag CCAAUUUAUCAUCCAAACA -3.3 -2.1 3.5 0 3 2 -31.1 84.4 2.7 8 Ib 31.6 70.8 101.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1087 NM_014176 Huesken HSPC150 29089 UUUGGAUGAUAAAUUGGAGug CUCCAAUUUAUCAUCCAAA -2.1 -0.9 4 1 5 2 -31.3 78.6 2 6 Ia 31.6 66.5 107.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1088 NM_014176 Huesken HSPC150 29089 GGAUGAUAAAUUGGAGUGAga UCACUCCAAUUUAUCAUCC -2.4 -3.3 4.5 0 -2 2 -34.1 55.1 -0.7 5 II 36.8 33.8 56.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1089 NM_014176 Huesken HSPC150 29089 AAAUUGGAGUGAGAAAUCGga CGAUUUCUCACUCCAAUUU -2.4 -0.9 0.9 2 4 2 -32.6 66.2 0 8 Ia 36.8 67.2 106.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1090 NM_014176 Huesken HSPC150 29089 AUUGGAGUGAGAAAUCGGAuc UCCGAUUUCUCACUCCAAU -2.4 -1.1 0.9 2 2 3 -36.5 54.2 -6.3 6 II 42.1 53.4 109.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1091 NM_014176 Huesken HSPC150 29089 AAAUCGGAUCUGAGGAGGUuc ACCUCCUCAGAUCCGAUUU -2.2 -0.9 1.3 0 3 3 -38.9 51.4 -6.6 6 II 47.4 53.3 100.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1092 NM_014176 Huesken HSPC150 29089 UCGGAUCUGAGGAGGUUCAaa UGAACCUCCUCAGAUCCGA -2.1 -2.4 0.1 0 -1 3 -41.4 52.7 -3.6 6 II 52.6 49.9 105.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1093 NM_014176 Huesken HSPC150 29089 CGGAUCUGAGGAGGUUCAAau UUGAACCUCCUCAGAUCCG -0.9 -2.4 -0.5 -1 -4 3 -39.9 43.3 -5.8 3 III 52.6 25.2 56.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1094 NM_014176 Huesken HSPC150 29089 GAGGUUCAAAUGGGUACCUcu AGGUACCCAUUUGAACCUC -2.1 -2.4 -1.2 -1 0 3 -38.1 49.8 -4 2 III 47.4 42.5 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1095 NM_014176 Huesken HSPC150 29089 UUCAAAUGGGUACCUCUCAgg UGAGAGGUACCCAUUUGAA -2.1 -0.9 0.5 2 0 3 -37.1 67.2 1.4 8 II 42.1 63.2 87.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1096 NM_014176 Huesken HSPC150 29089 CAAAUGGGUACCUCUCAGGaa CCUGAGAGGUACCCAUUUG -3.3 -2.1 -0.7 -1 1 3 -39.2 60.6 -6.7 6 II 52.6 58.3 78.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1097 NM_014176 Huesken HSPC150 29089 AUGGGUACCUCUCAGGAAUga AUUCCUGAGAGGUACCCAU -1.1 -1.1 -0.7 2 0 3 -39.7 60.1 -0.9 4 II 47.4 51.3 114.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1098 NM_014176 Huesken HSPC150 29089 ACCUCUCAGGAAUGAUAACuu GUUAUCAUUCCUGAGAGGU -2.2 -2.2 -0.7 1 1 2 -36.4 63.9 9.7 3 II 42.1 43.9 75.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1099 NM_014176 Huesken HSPC150 29089 CUCUCAGGAAUGAUAACUUcu AAGUUAUCAUUCCUGAGAG -0.9 -2.1 0.2 -1 -1 2 -33.9 65.5 -6.2 4 III 36.8 46.6 79.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1100 NM_014176 Huesken HSPC150 29089 AUGAUAACUUCUAGCUUAAaa UUAAGCUAGAAGUUAUCAU -0.9 -1.1 0.3 0 -1 2 -30.6 75.6 -5.7 7 II 26.3 49.3 89.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1101 NM_014176 Huesken HSPC150 29089 AAAACACCUUUCUCAUAAGgu CUUAUGAGAAAGGUGUUUU -2.1 -0.9 0.6 1 3 2 -30.8 76.8 -2.4 5 Ia 31.6 56.9 92.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1102 NM_014176 Huesken HSPC150 29089 CCUUUCUCAUAAGGUGUGUug ACACACCUUAUGAGAAAGG -2.2 -3.3 -1.9 -1 -2 2 -35.7 63.8 -3.7 4 II 42.1 35.9 74.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1103 NM_014176 Huesken HSPC150 29089 GUGUUGGCUCCACCUAAUAuu UAUUAGGUGGAGCCAACAC -1.3 -2.2 -1.8 0 -3 3 -38.3 54.2 -3.7 3 III 47.4 37.3 57.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1104 NM_014176 Huesken HSPC150 29089 CUCCACCUAAUAUUUGAGCuc GCUCAAAUAUUAGGUGGAG -3.4 -2.1 0.6 0 1 2 -35 71.3 10.4 3 II 42.1 53.7 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1105 NM_014176 Huesken HSPC150 29089 CACCUAAUAUUUGAGCUCGca CGAGCUCAAAUAUUAGGUG -2.4 -2.1 1.1 0 0 2 -34.1 65.2 1 4 II 42.1 54.3 90 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1106 NM_014176 Huesken HSPC150 29089 ACCUAAUAUUUGAGCUCGCag GCGAGCUCAAAUAUUAGGU -3.4 -2.2 1.8 1 3 3 -35.4 58.2 7.5 5 Ia 42.1 54 71.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1107 NM_014176 Huesken HSPC150 29089 UAAUAUUUGAGCUCGCAGGuc CCUGCGAGCUCAAAUAUUA -3.3 -1.3 2.4 2 4 3 -35.3 89.1 0.4 9 Ia 42.1 79.9 102.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1108 NM_014176 Huesken HSPC150 29089 AUAUUUGAGCUCGCAGGUCau GACCUGCGAGCUCAAAUAU -2.4 -1.1 2.1 2 4 3 -37.7 60.4 5.1 7 Ia 47.4 64.1 100.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1109 NM_014176 Huesken HSPC150 29089 UCGCAGGUCAUCCAUUUGGuc CCAAAUGGAUGACCUGCGA -3.3 -2.4 -0.6 2 2 3 -39.6 59.4 2.8 7 II 52.6 66.1 95.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1110 NM_014176 Huesken HSPC150 29089 GUCAUCCAUUUGGUCUUUAuc UAAAGACCAAAUGGAUGAC -1.3 -2.2 -1.1 0 -2 2 -33.7 66.3 -1.4 3 III 36.8 35.4 63.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1111 NM_014176 Huesken HSPC150 29089 GGUCUUUAUCUUGCCAACAug UGUUGGCAAGAUAAAGACC -2.1 -3.3 0.8 2 -2 3 -35.7 63.5 -0.7 3 II 42.1 42.6 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1112 NM_014176 Huesken HSPC150 29089 CUUGCCAACAUGUGAUGCCug GGCAUCACAUGUUGGCAAG -3.3 -2.1 -0.2 -1 2 3 -38.9 60.3 5.4 4 II 52.6 56.8 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1113 NM_014176 Huesken HSPC150 29089 UGCCAACAUGUGAUGCCUGgg CAGGCAUCACAUGUUGGCA -2.1 -2.1 -0.5 1 3 3 -40.1 50.1 2.4 4 II 52.6 56.7 90.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1114 NM_001001481 Huesken FLJ11011 55284 ACCAUUUUGUUUUCUUUGGau CCAAAGAAAACAAAAUGGU -3.3 -2.2 0.4 3 2 2 -30.1 94 3 6 Ia 31.6 62.7 101.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1115 NM_001001481 Huesken FLJ11011 55284 UUUGUUUUCUUUGGAUUCUug AGAAUCCAAAGAAAACAAA -2.1 -0.9 1.6 1 2 2 -29.4 92.1 -1 8 II 26.3 71.4 105.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1116 NM_001001481 Huesken FLJ11011 55284 UUUCUUUGGAUUCUUGUUAca UAACAAGAAUCCAAAGAAA -1.3 -0.9 1.6 3 1 2 -29.8 98.7 4 9 II 26.3 69.6 114.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1117 NM_001001481 Huesken FLJ11011 55284 UUCUUGUUACAUGUUCGCAca UGCGAACAUGUAACAAGAA -2.1 -0.9 0.5 1 2 3 -33.7 87.8 3.9 7 II 36.8 64.3 103.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1118 NM_001001481 Huesken FLJ11011 55284 UCUUGUUACAUGUUCGCACau GUGCGAACAUGUAACAAGA -2.2 -2.4 0.3 2 4 3 -35 85.3 9.7 7 Ia 42.1 71.5 125.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1119 NM_001001481 Huesken FLJ11011 55284 UUGUUACAUGUUCGCACAUaa AUGUGCGAACAUGUAACAA -1.1 -0.9 -1.4 -1 1 3 -33.7 70.6 1.5 5 II 36.8 56.1 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1120 NM_001001481 Huesken FLJ11011 55284 AAAAGAAUUAUCCGGUGGUcg ACCACCGGAUAAUUCUUUU -2.2 -0.9 0.1 0 3 4 -33.7 65.6 -3.9 7 II 36.8 58.8 96.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1121 NM_001001481 Huesken FLJ11011 55284 AAAGAAUUAUCCGGUGGUCgu GACCACCGGAUAAUUCUUU -2.4 -0.9 0.1 1 4 4 -35.2 57.6 5.4 6 Ia 42.1 56.7 96.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1122 NM_001001481 Huesken FLJ11011 55284 UAUCCGGUGGUCGUCUCUUuu AAGAGACGACCACCGGAUA -0.9 -1.3 -0.1 2 3 4 -40.5 59.1 -4 6 II 52.6 61 82.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1123 NM_001001481 Huesken FLJ11011 55284 UGGUCGUCUCUUUUCCUUGca CAAGGAAAAGAGACGACCA -2.1 -2.1 0.3 1 2 2 -37.1 82.6 5.4 6 II 47.4 68 109.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1124 NM_001001481 Huesken FLJ11011 55284 GGUCGUCUCUUUUCCUUGCag GCAAGGAAAAGAGACGACC -3.4 -3.3 2 2 1 2 -38.4 65.2 10.4 2 II 52.6 44 112.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1125 NM_001001481 Huesken FLJ11011 55284 UUUCCUUGCAGCUGGAAAGca CUUUCCAGCUGCAAGGAAA -2.1 -0.9 -3 2 3 2 -37.4 79.8 -2.4 6 Ia 47.4 68.8 103 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1126 NM_001001481 Huesken FLJ11011 55284 UCCUUGCAGCUGGAAAGCAug UGCUUUCCAGCUGCAAGGA -2.1 -2.4 -1.4 1 0 2 -41.1 44.5 -3.8 4 II 52.6 47.3 110.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1127 NM_001001481 Huesken FLJ11011 55284 AGCUGGAAAGCAUGCUAAUaa AUUAGCAUGCUUUCCAGCU -1.1 -2.1 -1.2 0 -1 2 -36.8 54 -6.3 3 II 42.1 39.8 67.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1128 NM_001001481 Huesken FLJ11011 55284 GGAAAGCAUGCUAAUAAUGcu CAUUAUUAGCAUGCUUUCC -2.1 -3.3 1.3 0 0 2 -32.5 58.5 0.8 3 II 36.8 46.6 93.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1129 NM_001001481 Huesken FLJ11011 55284 AAAGCAUGCUAAUAAUGCUaa AGCAUUAUUAGCAUGCUUU -2.1 -0.9 -2.5 3 3 2 -32.3 73.8 -1.7 4 II 31.6 60.5 84.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1130 NM_001001481 Huesken FLJ11011 55284 AAUGCUAAGACAAACUGAUug AUCAGUUUGUCUUAGCAUU -1.1 -0.9 -0.4 2 2 2 -32.3 71.1 -8.9 6 II 31.6 58.9 107 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1131 NM_001001481 Huesken FLJ11011 55284 AUGCUAAGACAAACUGAUUgg AAUCAGUUUGUCUUAGCAU -0.9 -1.1 -0.4 2 0 2 -32.3 67.5 -4.3 5 II 31.6 55 104.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1132 NM_001001481 Huesken FLJ11011 55284 CUAAGACAAACUGAUUGGAcu UCCAAUCAGUUUGUCUUAG -2.4 -2.1 0.6 -1 -1 2 -33.5 57.9 -5.1 4 II 36.8 41 85 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1133 NM_001001481 Huesken FLJ11011 55284 AGACAAACUGAUUGGACUGag CAGUCCAAUCAGUUUGUCU -2.1 -2.1 0.6 1 3 2 -35.6 61.9 8 5 Ia 42.1 56.4 121.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1134 NM_001001481 Huesken FLJ11011 55284 CUGAUUGGACUGAGAGCGCug GCGCUCUCAGUCCAAUCAG -3.4 -2.1 1.5 -2 1 4 -41 44.4 2.8 3 II 57.9 51.4 108.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1135 NM_001001481 Huesken FLJ11011 55284 GAGAGCGCUGGGGACCAGUcu ACUGGUCCCCAGCGCUCUC -2.2 -2.4 -2.7 0 -1 4 -46.6 31.7 -4 1 III 68.4 37.4 93.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1136 NM_001001481 Huesken FLJ11011 55284 GCGCUGGGGACCAGUCUUCug GAAGACUGGUCCCCAGCGC -2.4 -3.4 -2.7 1 -1 4 -45.4 28.4 0.1 2 II 68.4 36.9 80.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1137 NM_001001481 Huesken FLJ11011 55284 CGCUGGGGACCAGUCUUCUgu AGAAGACUGGUCCCCAGCG -2.1 -2.4 -2.7 -1 -2 4 -44.1 37.8 -6 1 III 63.2 34.2 88.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1138 NM_001001481 Huesken FLJ11011 55284 GGGGACCAGUCUUCUGUUAga UAACAGAAGACUGGUCCCC -1.3 -3.3 -1.5 1 -4 4 -40.6 46.7 -0.4 1 III 52.6 22.1 64.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1139 NM_001001481 Huesken FLJ11011 55284 GGACCAGUCUUCUGUUAGAau UCUAACAGAAGACUGGUCC -2.4 -3.3 -1.5 1 -2 2 -38.5 47.8 -6.1 1 III 47.4 27.4 73.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1140 NM_001001481 Huesken FLJ11011 55284 AGUCUUCUGUUAGAAUGGAua UCCAUUCUAACAGAAGACU -2.4 -2.1 0 3 1 2 -35 56.7 -3.8 4 II 36.8 42.4 64.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1141 NM_001001481 Huesken FLJ11011 55284 UCUUCUGUUAGAAUGGAUAaa UAUCCAUUCUAACAGAAGA -1.3 -2.4 0 0 0 2 -33.1 85.1 -4 7 II 31.6 59.3 83.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1142 NM_001001481 Huesken FLJ11011 55284 CUGUUAGAAUGGAUAAACAga UGUUUAUCCAUUCUAACAG -2.1 -2.1 0.2 -1 -2 2 -31.4 68.8 -6 4 II 31.6 45.1 66.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1143 NM_001001481 Huesken FLJ11011 55284 UUAGAAUGGAUAAACAGAUau AUCUGUUUAUCCAUUCUAA -1.1 -0.9 2.1 2 2 2 -30.6 70.3 -3.9 8 II 26.3 70.4 96.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1144 NM_001001481 Huesken FLJ11011 55284 UAGAAUGGAUAAACAGAUAug UAUCUGUUUAUCCAUUCUA -1.3 -1.3 2.1 0 -1 2 -31 73.5 -1.3 7 II 26.3 59.8 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1145 NM_001001481 Huesken FLJ11011 55284 UGACCAUUGCUAUAAACAUga AUGUUUAUAGCAAUGGUCA -1.1 -2.1 -0.2 3 1 2 -32.6 70.8 -4 5 II 31.6 58.1 96.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1146 NM_001001481 Huesken FLJ11011 55284 UUGCUAUAAACAUGAGGAUga AUCCUCAUGUUUAUAGCAA -1.1 -0.9 -0.2 1 1 2 -32.8 71.7 -6.3 7 II 31.6 57.7 104.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1147 NM_001001481 Huesken FLJ11011 55284 GCUAUAAACAUGAGGAUGAac UCAUCCUCAUGUUUAUAGC -2.4 -3.4 1.6 0 -2 2 -34.3 59 -6.3 6 II 36.8 39.5 78.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1148 NM_001001481 Huesken FLJ11011 55284 UAUAAACAUGAGGAUGAACag GUUCAUCCUCAUGUUUAUA -2.2 -1.3 1.6 0 3 2 -31.9 75.3 12.4 7 Ia 31.6 64.9 105.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1149 NM_001001481 Huesken FLJ11011 55284 UAAACAUGAGGAUGAACAGga CUGUUCAUCCUCAUGUUUA -2.1 -1.3 1.6 0 4 2 -33.7 73.7 0 7 Ia 36.8 66 112.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1150 NM_001001481 Huesken FLJ11011 55284 AACAUGAGGAUGAACAGGAau UCCUGUUCAUCCUCAUGUU -2.4 -0.9 1.6 2 1 2 -37.2 58.5 -6.3 7 II 42.1 58.7 108.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1151 NM_001001481 Huesken FLJ11011 55284 ACAUGAGGAUGAACAGGAAua UUCCUGUUCAUCCUCAUGU -0.9 -2.2 1.6 1 0 2 -37.2 44.2 -6.3 5 II 42.1 34.3 73 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1152 NM_001001481 Huesken FLJ11011 55284 AUGAGGAUGAACAGGAAUAuu UAUUCCUGUUCAUCCUCAU -1.3 -1.1 1.8 1 -1 2 -35.3 62.1 -6.4 6 II 36.8 55.3 104 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1153 NM_001001481 Huesken FLJ11011 55284 GGAUGAACAGGAAUAUUUUca AAAAUAUUCCUGUUCAUCC -0.9 -3.3 2.1 0 -1 2 -31.4 64.8 -4.2 4 II 31.6 39.3 53.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1154 NM_001001481 Huesken FLJ11011 55284 UGAACAGGAAUAUUUUCACca GUGAAAAUAUUCCUGUUCA -2.2 -2.1 1.1 0 4 2 -31.3 83.5 9.7 7 Ib 31.6 67.9 82 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1155 NM_001001481 Huesken FLJ11011 55284 AACAGGAAUAUUUUCACCAgu UGGUGAAAAUAUUCCUGUU -2.1 -0.9 0.5 1 2 2 -32.2 80.9 1.6 6 II 31.6 65.8 115.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1156 NM_001001481 Huesken FLJ11011 55284 ACAGGAAUAUUUUCACCAGua CUGGUGAAAAUAUUCCUGU -2.1 -2.2 0.5 1 3 2 -33.4 63.7 3 4 Ib 36.8 53.9 107.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1157 NM_001001481 Huesken FLJ11011 55284 AGGAAUAUUUUCACCAGUAaa UACUGGUGAAAAUAUUCCU -1.3 -2.1 0.5 1 -1 2 -32.6 68 -6 5 II 31.6 53.1 94.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1158 NM_001001481 Huesken FLJ11011 55284 GAAUAUUUUCACCAGUAAAca UUUACUGGUGAAAAUAUUC -0.9 -2.4 0.6 1 -2 2 -29 81.5 1.3 5 II 26.3 43.6 91.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1159 NM_001001481 Huesken FLJ11011 55284 UUCACCAGUAAACAUGACCug GGUCAUGUUUACUGGUGAA -3.3 -0.9 -1.1 0 3 2 -35.8 82 12.1 6 Ib 42.1 78.4 103.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1160 NM_001001481 Huesken FLJ11011 55284 GACCUGAGGAGAGUCAAAAgg UUUUGACUCUCCUCAGGUC -0.9 -2.4 -1 2 -2 2 -38.3 49.8 -1.4 3 III 47.4 35.1 95 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1161 NM_001001481 Huesken FLJ11011 55284 CUGAGGAGAGUCAAAAGGAua UCCUUUUGACUCUCCUCAG -2.4 -2.1 0.2 -1 -2 2 -38.2 41.5 -10.7 3 III 47.4 45.5 78.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1162 NM_001001481 Huesken FLJ11011 55284 GAGAGUCAAAAGGAUAUCGac CGAUAUCCUUUUGACUCUC -2.4 -2.4 1 0 1 2 -34.5 65.7 2.3 4 II 42.1 54.2 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1163 NM_001001481 Huesken FLJ11011 55284 AGAGUCAAAAGGAUAUCGAcu UCGAUAUCCUUUUGACUCU -2.4 -2.1 -0.3 1 2 2 -34.5 66.5 -4 6 II 36.8 52.9 74.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1164 NM_001001481 Huesken FLJ11011 55284 AGUCAAAAGGAUAUCGACUac AGUCGAUAUCCUUUUGACU -2.1 -2.1 -4.1 3 2 2 -34.3 67.5 3.8 4 II 36.8 56.1 81.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1165 NM_001001481 Huesken FLJ11011 55284 CAAAAGGAUAUCGACUACUaa AGUAGUCGAUAUCCUUUUG -2.1 -2.1 1.9 -1 -1 2 -33.2 58.7 -5.6 6 II 36.8 57.6 123.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1166 NM_001001481 Huesken FLJ11011 55284 UAUCGACUACUAAAUUUAAau UUAAAUUUAGUAGUCGAUA -0.9 -1.3 2.6 1 0 2 -27.7 76.3 -6.3 6 II 21.1 53.8 79.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1167 NM_001001481 Huesken FLJ11011 55284 AUCGACUACUAAAUUUAAAua UUUAAAUUUAGUAGUCGAU -0.9 -1.1 2.9 3 0 2 -27.3 82.5 1 5 II 21.1 51.3 88 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1168 NM_001001481 Huesken FLJ11011 55284 GACUACUAAAUUUAAAUAGaa CUAUUUAAAUUUAGUAGUC -2.1 -2.4 -0.9 1 0 1 -25.9 92.5 5.7 6 II 21.1 54.7 83.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1169 NM_001001481 Huesken FLJ11011 55284 CUAAAUUUAAAUAGAAGUUga AACUUCUAUUUAAAUUUAG -0.9 -2.1 1 -1 -1 1 -24.2 89.4 -0.5 6 II 15.8 57.8 96.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1170 NM_001001481 Huesken FLJ11011 55284 UUAAAUAGAAGUUGAAAUUuu AAUUUCAACUUCUAUUUAA -0.9 -0.9 4.1 -1 1 1 -25.3 96.5 1.8 9 II 15.8 72.6 97.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1171 NM_001001481 Huesken FLJ11011 55284 UUCCCCUUCAUAUAAGGUAcc UACCUUAUAUGAAGGGGAA -1.3 -0.9 -3.1 3 0 4 -35.3 77.2 -3.8 5 II 36.8 62.4 111.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1172 NM_001001481 Huesken FLJ11011 55284 AUAUAAGGUACCUGGUGCAcc UGCACCAGGUACCUUAUAU -2.1 -1.1 0.7 0 2 2 -37.4 60.7 -5.8 8 II 42.1 53.4 78 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1173 NM_001001481 Huesken FLJ11011 55284 UAAGGUACCUGGUGCACCUuc AGGUGCACCAGGUACCUUA -2.1 -1.3 -6.5 0 3 2 -41.5 60.9 -4 5 II 52.6 66.3 93.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1174 NM_001001481 Huesken FLJ11011 55284 UACCUGGUGCACCUUCCAUgu AUGGAAGGUGCACCAGGUA -1.1 -1.3 -1.5 2 2 2 -41.5 63.3 0.7 5 II 52.6 54.6 86.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1175 NM_001001481 Huesken FLJ11011 55284 CUGGUGCACCUUCCAUGUCua GACAUGGAAGGUGCACCAG -2.4 -2.1 -1.5 0 0 2 -41.4 49.3 10.8 0 II 57.9 47 94.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1176 NM_001001481 Huesken FLJ11011 55284 GGUGCACCUUCCAUGUCUAca UAGACAUGGAAGGUGCACC -1.3 -3.3 0.2 0 -1 2 -40.6 45.7 -8.7 1 III 52.6 24.8 38.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1177 NM_001001481 Huesken FLJ11011 55284 CAUGUCUACAAUCCACUGUgu ACAGUGGAUUGUAGACAUG -2.2 -2.1 0 1 -1 2 -36 77.8 1.8 6 II 42.1 53 110.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1178 NM_001001481 Huesken FLJ11011 55284 AUGUCUACAAUCCACUGUGua CACAGUGGAUUGUAGACAU -2.1 -1.1 -0.1 1 3 2 -36 76.6 0.1 6 Ia 42.1 68.4 115.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1179 NM_001001481 Huesken FLJ11011 55284 UGUCUACAAUCCACUGUGUaa ACACAGUGGAUUGUAGACA -2.2 -2.1 -0.1 1 1 2 -37.1 64.6 -11.3 6 II 42.1 50.9 99.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1180 NM_001001481 Huesken FLJ11011 55284 UCUACAAUCCACUGUGUAAuu UUACACAGUGGAUUGUAGA -0.9 -2.4 -1.1 0 -1 2 -35 76.6 -3.8 6 II 36.8 47.8 92.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1181 NM_001001481 Huesken FLJ11011 55284 UACAAUCCACUGUGUAAUUga AAUUACACAGUGGAUUGUA -0.9 -1.3 -0.1 -1 0 2 -32.5 77.6 -1.3 6 II 31.6 57.8 111.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1182 NM_001001481 Huesken FLJ11011 55284 CACUGUGUAAUUGAAUUUUga AAAAUUCAAUUACACAGUG -0.9 -2.1 2.8 -1 -3 1 -28.4 78.7 -3 5 III 26.3 48.9 76.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1183 NM_001001481 Huesken FLJ11011 55284 GUGUAAUUGAAUUUUGAACac GUUCAAAAUUCAAUUACAC -2.2 -2.2 2.1 2 1 1 -27.5 95.7 17.8 5 II 26.3 55.2 73.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1184 NM_001001481 Huesken FLJ11011 55284 AUUGAAUUUUGAACACUCUuc AGAGUGUUCAAAAUUCAAU -2.1 -1.1 -1.8 2 2 1 -29.7 78.7 -3.9 6 II 26.3 63.7 109.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1185 NM_001001481 Huesken FLJ11011 55284 UUGAAUUUUGAACACUCUUcu AAGAGUGUUCAAAAUUCAA -0.9 -0.9 -1.8 1 1 1 -29.5 89.3 3.4 6 II 26.3 73.7 113.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1186 NM_001001481 Huesken FLJ11011 55284 AAUUUUGAACACUCUUCUCau GAGAAGAGUGUUCAAAAUU -2.4 -0.9 0.2 1 4 1 -31 92.9 7.4 7 Ia 31.6 67.5 115.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1187 NM_001001481 Huesken FLJ11011 55284 CUCUUCUCAUUUAAGGUCAuu UGACCUUAAAUGAGAAGAG -2.1 -2.1 0.3 0 -3 2 -33.7 76.9 -5.3 5 II 36.8 48.8 75 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1188 NM_001001481 Huesken FLJ11011 55284 UCUUCUCAUUUAAGGUCAUuc AUGACCUUAAAUGAGAAGA -1.1 -2.4 0.3 -1 1 2 -32.7 70.6 -6.6 5 II 31.6 48.9 68.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1189 NM_001001481 Huesken FLJ11011 55284 CUCAUUUAAGGUCAUUCCAgg UGGAAUGACCUUAAAUGAG -2.1 -2.1 0 0 -2 2 -33.6 79.1 -0.3 4 II 36.8 50.4 96.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1190 NM_001001481 Huesken FLJ11011 55284 UUUAAGGUCAUUCCAGGAGgu CUCCUGGAAUGACCUUAAA -2.1 -0.9 0 1 4 2 -35.8 77.3 8.1 9 Ia 42.1 71.4 100.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1191 NM_001001481 Huesken FLJ11011 55284 UUAAGGUCAUUCCAGGAGGug CCUCCUGGAAUGACCUUAA -3.3 -0.9 -0.8 1 4 2 -38.2 67.1 0.1 7 Ia 47.4 74.7 99.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1192 NM_016021 Huesken UBE2J1 51465 AAUAUGUAUUCGUUUGCCAga UGGCAAACGAAUACAUAUU -2.1 -0.9 1.5 2 3 3 -31.7 85.3 -3.8 7 II 31.6 61 110 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1193 NM_016021 Huesken UBE2J1 51465 UGUAUUCGUUUGCCAGAUAua UAUCUGGCAAACGAAUACA -1.3 -2.1 1.2 0 -1 3 -34.2 70.5 -1.4 6 II 36.8 50.6 91.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1194 NM_016021 Huesken UBE2J1 51465 AUUCGUUUGCCAGAUAUAUuc AUAUAUCUGGCAAACGAAU -1.1 -1.1 1.2 4 1 3 -32.1 73 -6.3 6 II 31.6 56.1 95.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1195 NM_016021 Huesken UBE2J1 51465 AUUCGUCGGAAUAUAAGAGcu CUCUUAUAUUCCGACGAAU -2.1 -1.1 0.6 3 5 3 -32.7 74.9 5.1 5 Ib 36.8 60.5 98.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1196 NM_016021 Huesken UBE2J1 51465 CUGCCAAUGCCAAAGUCAGga CUGACUUUGGCAUUGGCAG -2.1 -2.1 -0.9 1 0 3 -38.6 46.8 -6.9 2 II 52.6 45.7 76.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1197 NM_016021 Huesken UBE2J1 51465 GGAUGACAAUCAGUACAGCug GCUGUACUGAUUGUCAUCC -3.4 -3.3 1.2 0 2 2 -37.5 45.8 7.4 2 II 47.4 37.5 62.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1198 NM_016021 Huesken UBE2J1 51465 CAGUACAGCUGACCCACCAug UGGUGGGUCAGCUGUACUG -2.1 -2.1 -0.4 0 -2 3 -42.6 48.8 -0.7 3 II 57.9 42.4 83.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1199 NM_016021 Huesken UBE2J1 51465 GGUUGUCUCUUGGCUGGUGgc CACCAGCCAAGAGACAACC -2.1 -3.3 1 1 3 -41.2 49 0 1 II 57.9 35 55.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1200 NM_016021 Huesken UBE2J1 51465 UUGGCUGGUGGCCCUGGAUua AUCCAGGGCCACCAGCCAA -1.1 -0.9 -3.8 0 1 5 -45.8 51.8 -3.9 3 II 63.2 52.6 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1201 NM_016021 Huesken UBE2J1 51465 ACAUCUGGUGAAGUAGACAac UGUCUACUUCACCAGAUGU -2.1 -2.2 -1 1 1 2 -37.3 60 0.9 4 II 42.1 50 73.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1202 NM_016021 Huesken UBE2J1 51465 GAAGUAGACAACCUUCUCUga AGAGAAGGUUGUCUACUUC -2.1 -2.4 -2.4 1 1 2 -36.1 68.7 0.7 5 II 42.1 52.1 78.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1203 NM_016021 Huesken UBE2J1 51465 ACUCUGCUGCUGGGCCCGGcg CCGGGCCCAGCAGCAGAGU -3.3 -2.2 -0.7 2 4 8 -48.4 26.1 0 3 II 73.7 44.4 47.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1204 NM_016021 Huesken UBE2J1 51465 CUGCUGCUGGGCCCGGCGCug GCGCCGGGCCCAGCAGCAG -3.4 -2.1 -0.8 1 1 11 -50.9 29.8 5.5 1 II 84.2 43.6 35.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1205 NM_016021 Huesken UBE2J1 51465 UUCUUAGCUACAGGUUGGGua CCCAACCUGUAGCUAAGAA -3.3 -0.9 1 -1 4 3 -38 63.6 -2.4 8 Ia 47.4 63.9 78.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1206 NM_016021 Huesken UBE2J1 51465 AGGUUGGGUAGGUUGAUGAaa UCAUCAACCUACCCAACCU -2.4 -2.1 1 0 3 -39.3 67.9 -1.4 7 II 47.4 49.4 47.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1207 NM_016021 Huesken UBE2J1 51465 UGGGUAGGUUGAUGAAAGGau CCUUUCAUCAACCUACCCA -3.3 -2.1 4.4 -1 2 3 -38 54.1 0 5 II 47.4 56.6 56.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1208 NM_016021 Huesken UBE2J1 51465 UGGCCGUAGCACCCUGGAAug UUCCAGGGUGCUACGGCCA -0.9 -2.1 -2.9 3 -1 5 -45.2 45.6 -1.4 2 II 63.2 41 75.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1209 NM_016021 Huesken UBE2J1 51465 GGUAUAUCAUCUUGUAAAUca AUUUACAAGAUGAUAUACC -1.1 -3.3 2.2 0 -2 2 -29.8 79.5 -3.3 4 II 26.3 33.6 47.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1210 NM_016021 Huesken UBE2J1 51465 UUGUAAAUCAGUUAGUGAAaa UUCACUAACUGAUUUACAA -0.9 -0.9 0.6 1 0 1 -30.1 91.1 2 8 II 26.3 61.4 67.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1211 NM_016021 Huesken UBE2J1 51465 AGUGGUUUAAGUCUGACUCag GAGUCAGACUUAAACCACU -2.4 -2.1 0.1 2 4 2 -35.9 83.7 15.2 5 Ib 42.1 65.3 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1212 NM_016021 Huesken UBE2J1 51465 UUCCAGAUGAAUUGACUUCug GAAGUCAAUUCAUCUGGAA -2.4 -0.9 -0.5 1 2 2 -33.8 80.2 15.4 8 Ib 36.8 71.6 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1213 NM_016021 Huesken UBE2J1 51465 UCCAGAUGAAUUGACUUCUgc AGAAGUCAAUUCAUCUGGA -2.1 -2.4 -0.7 1 0 2 -35 72.8 -1 7 II 36.8 63.2 79.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1214 NM_016021 Huesken UBE2J1 51465 CCAGAUGAAUUGACUUCUGcc CAGAAGUCAAUUCAUCUGG -2.1 -3.3 -1.7 -1 0 2 -34.7 52.1 -1.9 2 II 42.1 47.2 60.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1215 NM_016021 Huesken UBE2J1 51465 CAGAUGAAUUGACUUCUGCcu GCAGAAGUCAAUUCAUCUG -3.4 -2.1 -0.7 -1 1 2 -34.8 71.7 10.1 5 II 42.1 57.5 54.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1216 NM_016021 Huesken UBE2J1 51465 CUGCCUUAAAGCUUAUUUGcc CAAAUAAGCUUUAAGGCAG -2.1 -2.1 -2.4 1 0 3 -31.8 85.3 -2 3 II 36.8 58.1 56 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1217 NM_016021 Huesken UBE2J1 51465 GUUCUUUGGCUUCUUGGUCag GACCAAGAAGCCAAAGAAC -2.4 -2.2 3 3 3 -36.6 72.8 15.2 4 II 47.4 53.3 56.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1218 NM_016021 Huesken UBE2J1 51465 UCUUUGGCUUCUUGGUCAGcu CUGACCAAGAAGCCAAAGA -2.1 -2.4 1 -1 3 3 -37.7 70 0.7 7 Ib 47.4 55 73.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1219 NM_016021 Huesken UBE2J1 51465 GCUUCCAGAUUUUAAAGGCaa GCCUUUAAAAUCUGGAAGC -3.4 -3.4 -0.1 0 2 3 -34.4 69.2 10.4 3 II 42.1 46 50.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1220 NM_016021 Huesken UBE2J1 51465 UUCCAGAUUUUAAAGGCAAca UUGCCUUUAAAAUCUGGAA -0.9 -0.9 -0.1 1 0 3 -31.9 63.9 -3.6 6 II 31.6 58.3 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1221 NM_016021 Huesken UBE2J1 51465 UCCAGAUUUUAAAGGCAACag GUUGCCUUUAAAAUCUGGA -2.2 -2.4 -0.1 0 1 3 -33.2 67.4 7.1 5 Ib 36.8 57.6 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1222 NM_016021 Huesken UBE2J1 51465 GCAAGUGCUCUUCUUUCCUca AGGAAAGAAGAGCACUUGC -2.1 -3.4 0.2 0 1 2 -37.8 61 3.8 3 III 47.4 44.1 70.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1223 NM_016021 Huesken UBE2J1 51465 AACCUAUGGCUCCCUCUCCuu GGAGAGGGAGCCAUAGGUU -3.3 -0.9 -0.7 4 3 3 -43.1 59 7.5 5 Ia 57.9 62.3 61 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1224 NM_016021 Huesken UBE2J1 51465 UGGCUCCCUCUCCUUUUGUug ACAAAAGGAGAGGGAGCCA -2.2 -2.1 -0.9 1 1 3 -41.3 64.9 -1.6 5 II 52.6 52.3 41.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1225 NM_016021 Huesken UBE2J1 51465 CCCUCUCCUUUUGUUGGCAua UGCCAACAAAAGGAGAGGG -2.1 -3.3 -0.2 -1 -2 3 -39.8 55.7 -0.4 1 III 52.6 30.2 28.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1226 NM_016021 Huesken UBE2J1 51465 UGAUGGCUAAUAAUGCUGUcc ACAGCAUUAUUAGCCAUCA -2.2 -2.1 0 0 2 3 -35 72.3 -4.2 7 II 36.8 63.1 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1227 NM_016021 Huesken UBE2J1 51465 UGGCUAAUAAUGCUGUCCUua AGGACAGCAUUAUUAGCCA -2.1 -2.1 0 1 2 3 -37.2 73.4 0.8 6 II 42.1 63.8 74.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1228 NM_016021 Huesken UBE2J1 51465 UAAUGCUGUCCUUAUACUCca GAGUAUAAGGACAGCAUUA -2.4 -1.3 0.7 1 4 2 -34.3 87 8.1 7 Ia 36.8 76.1 91.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1229 NM_016021 Huesken UBE2J1 51465 AGGAUGAUGGCCUGAGAUGcu CAUCUCAGGCCAUCAUCCU -2.1 -2.1 0.2 1 1 4 -40.9 52.6 -4.7 5 Ib 52.6 52.7 64.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1230 NM_016021 Huesken UBE2J1 51465 AUGAUGGCCUGAGAUGCUCaa GAGCAUCUCAGGCCAUCAU -2.4 -1.1 -0.5 2 3 4 -41 55 7.4 6 Ib 52.6 61.4 64.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1231 NM_016021 Huesken UBE2J1 51465 UGGCCUGAGAUGCUCAAACag GUUUGAGCAUCUCAGGCCA -2.2 -2.1 -5.3 2 2 4 -40.4 64 12.1 4 II 52.6 63.5 72.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1232 NM_016021 Huesken UBE2J1 51465 CCUGAGAUGCUCAAACAGAuu UCUGUUUGAGCAUCUCAGG -2.4 -3.3 -2 0 -3 2 -38.2 39.2 -8 2 III 47.4 38.8 56 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1233 NM_016021 Huesken UBE2J1 51465 CCCACUUCAAAUCGACCAUua AUGGUCGAUUUGAAGUGGG -1.1 -3.3 1.6 -1 -3 3 -37.2 62.4 1.8 3 III 47.4 34.6 56.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1234 NM_016021 Huesken UBE2J1 51465 CACUUCAAAUCGACCAUUAgc UAAUGGUCGAUUUGAAGUG -1.3 -2.1 1.6 -1 -4 2 -32.8 68.4 -10.7 5 II 36.8 41.4 46.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1235 NM_016021 Huesken UBE2J1 51465 AAUCGACCAUUAGCCGUUAgg UAACGGCUAAUGGUCGAUU -1.3 -0.9 -4.2 2 0 4 -35.7 51.1 -3.8 4 II 42.1 42.4 84 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1236 NM_016021 Huesken UBE2J1 51465 UAAUGCUUGGUGGUUUCAUgg AUGAAACCACCAAGCAUUA -1.1 -1.3 1.7 2 3 2 -34.4 78 -1.6 7 II 36.8 62.4 68.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1237 NM_016021 Huesken UBE2J1 51465 CAUGGGAUACUCUGGUGGCag GCCACCAGAGUAUCCCAUG -3.4 -2.1 1.9 -2 2 3 -41.9 48.5 3.1 2 II 57.9 49.6 53.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1238 NM_016021 Huesken UBE2J1 51465 ACUAUCCGCCCGUGAUAAAcu UUUAUCACGGGCGGAUAGU -0.9 -2.2 -1.2 1 -1 7 -38.1 54.2 -6.1 4 II 47.4 31.6 51.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1239 NM_016021 Huesken UBE2J1 51465 ACUCCUCCAUCAAAAUCGGag CCGAUUUUGAUGGAGGAGU -3.3 -2.2 0.1 2 4 3 -37.4 54.8 -4.9 3 II 47.4 51.4 48 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1240 NM_016021 Huesken UBE2J1 51465 GGCUGCGCAUGGUAAUGAUcu AUCAUUACCAUGCGCAGCC -1.1 -3.3 1.5 0 -2 4 -39.8 48 -4 2 III 52.6 21.7 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1241 NM_005339 Huesken HIP2 3093 GAGCUGUCUGUUUGAACAUuu AUGUUCAAACAGACAGCUC -1.1 -2.4 -1 1 -1 2 -35.7 59 -1 2 III 42.1 40 64.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1242 NM_005339 Huesken HIP2 3093 CUGUCUGUUUGAACAUUUCgg GAAAUGUUCAAACAGACAG -2.4 -2.1 -1 -1 -1 1 -32 76.5 2.8 3 II 36.8 54.6 76.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1243 NM_005339 Huesken HIP2 3093 UCUGUUUGAACAUUUCGGGau CCCGAAAUGUUCAAACAGA -3.3 -2.4 0.4 1 5 4 -34.6 81.9 0 7 Ia 42.1 71.6 92.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1244 NM_005339 Huesken HIP2 3093 UUUGAACAUUUCGGGAUUUug AAAUCCCGAAAUGUUCAAA -0.9 -0.9 0.9 -1 1 4 -31.1 64.6 -3.6 7 II 31.6 56.5 73.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1245 NM_005339 Huesken HIP2 3093 UUUCGGGAUUUUGUUUGUAcu UACAAACAAAAUCCCGAAA -1.3 -0.9 1 2 4 -31.1 71.6 1.6 6 II 31.6 57.2 66.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1246 NM_005339 Huesken HIP2 3093 UUCGGGAUUUUGUUUGUACug GUACAAACAAAAUCCCGAA -2.2 -0.9 1.2 0 3 4 -32.4 81.7 9.7 6 II 36.8 69.2 73.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1247 NM_005339 Huesken HIP2 3093 CGGGAUUUUGUUUGUACUGau CAGUACAAACAAAAUCCCG -2.1 -2.4 1 -1 -1 4 -33.3 65.6 3.7 2 II 42.1 50.1 70.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1248 NM_005339 Huesken HIP2 3093 UUGUUUGUACUGAUUUGCUac AGCAAAUCAGUACAAACAA -2.1 -0.9 0.9 0 3 2 -31.9 89.4 -4.2 7 II 31.6 71.4 77.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1249 NM_005339 Huesken HIP2 3093 UUGUACUGAUUUGCUACUAca UAGUAGCAAAUCAGUACAA -1.3 -0.9 0.8 1 0 2 -32.7 79.5 2 7 II 31.6 60.1 87.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1250 NM_005339 Huesken HIP2 3093 UGUACUGAUUUGCUACUACag GUAGUAGCAAAUCAGUACA -2.2 -2.1 0.8 0 3 2 -34 82.2 12.1 7 Ib 36.8 64.6 92.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1251 NM_005339 Huesken HIP2 3093 ACUGAUUUGCUACUACAGCau GCUGUAGUAGCAAAUCAGU -3.4 -2.2 -2 3 4 2 -36 68.1 14.8 4 Ia 42.1 63.3 87.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1252 NM_005339 Huesken HIP2 3093 GAUUUGCUACUACAGCAUCcu GAUGCUGUAGUAGCAAAUC -2.4 -2.4 -3 0 1 2 -35.2 66 9.8 3 II 42.1 49.7 65.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1253 NM_005339 Huesken HIP2 3093 UUUGCUACUACAGCAUCCUgu AGGAUGCUGUAGUAGCAAA -2.1 -0.9 -3 0 3 2 -37.1 72.7 -6.3 6 II 42.1 71.9 92.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1254 NM_005339 Huesken HIP2 3093 UUGCUACUACAGCAUCCUGug CAGGAUGCUGUAGUAGCAA -2.1 -0.9 -3 1 3 2 -38.3 66.2 4.7 4 Ib 47.4 63.1 93 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1255 NM_005339 Huesken HIP2 3093 UGCUACUACAGCAUCCUGUgg ACAGGAUGCUGUAGUAGCA -2.2 -2.1 -2.4 2 1 2 -39.6 76.3 -3.9 7 II 47.4 62.8 89.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1256 NM_005339 Huesken HIP2 3093 CUACAGCAUCCUGUGGAUCau GAUCCACAGGAUGCUGUAG -2.4 -2.1 -2.7 0 1 2 -39.8 50.5 11.1 2 II 52.6 48.5 67.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1257 NM_005339 Huesken HIP2 3093 AGCAUCCUGUGGAUCAUCUgg AGAUGAUCCACAGGAUGCU -2.1 -2.1 -1.7 2 1 2 -39.8 68.4 -4.2 4 II 47.4 49.3 68 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1258 NM_005339 Huesken HIP2 3093 CAUCCUGUGGAUCAUCUGGcu CCAGAUGAUCCACAGGAUG -3.3 -2.1 -1.7 1 1 2 -39.7 67.1 5.7 3 II 52.6 53.5 66.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1259 NM_005339 Huesken HIP2 3093 AUCCUGUGGAUCAUCUGGCuc GCCAGAUGAUCCACAGGAU -3.4 -1.1 -1 4 5 3 -41 63.6 4.8 5 Ib 52.6 68.5 74.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1260 NM_005339 Huesken HIP2 3093 UGUGGAUCAUCUGGCUCUGca CAGAGCCAGAUGAUCCACA -2.1 -2.1 1.3 0 3 3 -40.8 54.3 0.7 5 Ib 52.6 55 82.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1261 NM_005339 Huesken HIP2 3093 AUCUGGCUCUGCAGCUGCCaa GGCAGCUGCAGAGCCAGAU -3.3 -1.1 -3.5 1 4 3 -45 49 2.5 2 II 63.2 54.3 81.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1262 NM_005339 Huesken HIP2 3093 UGGCUCUGCAGCUGCCAAUag AUUGGCAGCUGCAGAGCCA -1.1 -2.1 -3.6 2 -1 3 -43.5 58.2 -6.3 4 II 57.9 50.7 85 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1263 NM_005339 Huesken HIP2 3093 CUCUGCAGCUGCCAAUAGUgc ACUAUUGGCAGCUGCAGAG -2.2 -2.1 -1.3 0 -2 3 -40.3 53.8 -5.9 2 III 52.6 40.1 62 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1264 NM_005339 Huesken HIP2 3093 UAGUGCUUGCAAUGACAAUaa AUUGUCAUUGCAAGCACUA -1.1 -1.3 -0.5 1 0 2 -34.5 73.6 -1.7 6 II 36.8 55.4 85.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1265 NM_005339 Huesken HIP2 3093 AGUGCUUGCAAUGACAAUAau UAUUGUCAUUGCAAGCACU -1.3 -2.1 -0.5 3 -1 2 -34.5 74.2 1.6 5 II 36.8 54 89.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1266 NM_005339 Huesken HIP2 3093 UGACAAUAAUACCGUGCGGag CCGCACGGUAUUAUUGUCA -3.3 -2.1 -0.3 1 4 4 -36.7 58.2 5.1 6 Ia 47.4 58.9 63.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1267 NM_005339 Huesken HIP2 3093 AUACCGUGCGGAGAGUCAUug AUGACUCUCCGCACGGUAU -1.1 -1.1 -0.4 4 2 4 -40.5 50 -4 5 II 52.6 51.5 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1268 NM_005339 Huesken HIP2 3093 UGCGGAGAGUCAUUGCAGCug GCUGCAAUGACUCUCCGCA -3.4 -2.1 0 1 3 4 -42 49.5 7.4 3 II 57.9 57.1 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1269 NM_005339 Huesken HIP2 3093 GGAGAGUCAUUGCAGCUGCcc GCAGCUGCAAUGACUCUCC -3.4 -3.3 -1.3 1 1 2 -41.7 44.9 12.5 2 II 57.9 46.8 47.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1270 NM_005339 Huesken HIP2 3093 GAGAGUCAUUGCAGCUGCCca GGCAGCUGCAAUGACUCUC -3.3 -2.4 -1.3 -1 2 3 -41.7 46.1 2.5 0 II 57.9 45 57.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1271 NM_005339 Huesken HIP2 3093 GAGUCAUUGCAGCUGCCCAuu UGGGCAGCUGCAAUGACUC -2.1 -2.4 -1.3 2 0 4 -42.6 57.6 3.3 1 II 57.9 38.7 44.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1272 NM_005339 Huesken HIP2 3093 AUUGCAGCUGCCCAUUGAUcu AUCAAUGGGCAGCUGCAAU -1.1 -1.1 -1.3 1 2 4 -39 57.3 -6.3 4 II 47.4 47.7 48.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1273 NM_005339 Huesken HIP2 3093 GCUGCCCAUUGAUCUUUCAgg UGAAAGAUCAAUGGGCAGC -2.1 -3.4 0.5 0 -2 4 -38.1 58 -3.8 2 III 47.4 28.5 57.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1274 NM_005339 Huesken HIP2 3093 CUGCCCAUUGAUCUUUCAGga CUGAAAGAUCAAUGGGCAG -2.1 -2.1 0.4 0 1 4 -36.8 73.3 8.1 2 II 47.4 49.4 79.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1275 NM_005339 Huesken HIP2 3093 UCUUUCAGGAUAUCCAAACaa GUUUGGAUAUCCUGAAAGA -2.2 -2.4 -1 1 2 2 -33.9 82.9 7.4 7 Ia 36.8 69.9 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1276 NM_005339 Huesken HIP2 3093 CUUUCAGGAUAUCCAAACAaa UGUUUGGAUAUCCUGAAAG -2.1 -2.1 -1 -1 -2 2 -33.6 71.6 2 3 II 36.8 42.4 58.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1277 NM_005339 Huesken HIP2 3093 UUCAGGAUAUCCAAACAAAua UUUGUUUGGAUAUCCUGAA -0.9 -0.9 -1 0 -1 2 -32.4 67.3 -11 5 II 31.6 56.7 78.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1278 NM_005339 Huesken HIP2 3093 UAUCCAAACAAAUAGCCCCug GGGGCUAUUUGUUUGGAUA -3.3 -1.3 -0.5 2 5 5 -35.9 79.3 9.7 7 Ia 42.1 80.5 81.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1279 NM_005339 Huesken HIP2 3093 AUCCAAACAAAUAGCCCCUgu AGGGGCUAUUUGUUUGGAU -2.1 -1.1 -0.5 1 2 5 -36.7 61.8 1.5 6 II 42.1 58.6 71 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1280 NM_005339 Huesken HIP2 3093 AAUAGCCCCUGUGACGGAAcu UUCCGUCACAGGGGCUAUU -0.9 -0.9 -2.1 2 1 5 -40.8 53.5 -0.7 4 II 52.6 39.4 55.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1281 NM_005339 Huesken HIP2 3093 UGACGGAACUAAUAUUAGGau CCUAAUAUUAGUUCCGUCA -3.3 -2.1 1 2 3 3 -33.3 69.6 2.3 5 II 36.8 67.6 74.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1282 NM_005339 Huesken HIP2 3093 ACGGAACUAAUAUUAGGAUgc AUCCUAAUAUUAGUUCCGU -1.1 -2.2 1 1 1 3 -32.3 63.4 1.1 4 II 31.6 43.7 53.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1283 NM_005339 Huesken HIP2 3093 AACUAAUAUUAGGAUGCCAua UGGCAUCCUAAUAUUAGUU -2.1 -0.9 1 2 1 3 -32.9 69.9 1.3 6 II 31.6 52.7 61.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1284 NM_005339 Huesken HIP2 3093 UAUUAGGAUGCCAUAUUUUag AAAAUAUGGCAUCCUAAUA -0.9 -1.3 1.2 0 2 3 -30.6 83.4 -6.2 9 II 26.3 67 67.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1285 NM_005339 Huesken HIP2 3093 UAGGAUGCCAUAUUUUAGUga ACUAAAAUAUGGCAUCCUA -2.2 -1.3 1.2 1 2 3 -32.9 84.5 1.1 7 II 31.6 71.8 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1286 NM_005339 Huesken HIP2 3093 CAUAUUUUAGUGAUAAACCgg GGUUUAUCACUAAAAUAUG -3.3 -2.1 1 0 2 2 -28.1 93.3 5.1 5 II 26.3 71.4 81.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1287 NM_005339 Huesken HIP2 3093 UAUUUUAGUGAUAAACCGGac CCGGUUUAUCACUAAAAUA -3.3 -1.3 0.7 0 5 4 -30.6 90 2.7 8 Ia 31.6 80.7 89.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1288 NM_005339 Huesken HIP2 3093 AUUUUAGUGAUAAACCGGAcc UCCGGUUUAUCACUAAAAU -2.4 -1.1 0.7 2 2 4 -31.7 70.3 -6.3 8 II 31.6 60.7 73 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1289 NM_005339 Huesken HIP2 3093 AUUAAAUGGGUAUGUUUCUgg AGAAACAUACCCAUUUAAU -2.1 -1.1 3.1 2 2 3 -30.1 79.4 -1.3 8 II 26.3 62 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1290 NM_005339 Huesken HIP2 3093 UAAAUGGGUAUGUUUCUGGua CCAGAAACAUACCCAUUUA -3.3 -1.3 3.1 0 5 3 -33.5 86.6 2.3 10 Ia 36.8 81.1 72.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1291 NM_005339 Huesken HIP2 3093 AUGGGUAUGUUUCUGGUAUuu AUACCAGAAACAUACCCAU -1.1 -1.1 4.4 2 1 3 -35 75.1 3.8 5 II 36.8 54.8 76.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1292 NM_005339 Huesken HIP2 3093 UUUUAUCUCUAGUUGGUAUcu AUACCAACUAGAGAUAAAA -1.1 -0.9 2.8 1 2 2 -30.6 101.7 3.4 8 II 26.3 62.2 78.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1293 NM_005339 Huesken HIP2 3093 UCUAGUUGGUAUCUUCCUCcu GAGGAAGAUACCAACUAGA -2.4 -2.4 -0.9 2 4 2 -36.6 83.3 17.5 6 Ia 42.1 67.7 79.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1294 NM_005339 Huesken HIP2 3093 UAGUUGGUAUCUUCCUCCUuc AGGAGGAAGAUACCAACUA -2.1 -1.3 -0.9 0 2 2 -37.5 82 -3.3 7 II 42.1 66.4 75.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1295 NM_005339 Huesken HIP2 3093 AGUUGGUAUCUUCCUCCUUca AAGGAGGAAGAUACCAACU -0.9 -2.1 -0.9 2 1 2 -37.1 67.6 1.5 5 II 42.1 51.2 68.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1296 NM_005339 Huesken HIP2 3093 UUGGUAUCUUCCUCCUUCAua UGAAGGAGGAAGAUACCAA -2.1 -0.9 -0.9 1 0 2 -37.3 76.8 -8.5 7 II 42.1 64.7 82.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1297 NM_005339 Huesken HIP2 3093 CUUCCUCCUUCAUAUGGUGug CACCAUAUGAAGGAGGAAG -2.1 -2.1 -0.5 0 1 2 -37.2 62.4 -4.4 2 II 47.4 47.1 69.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1298 NM_005339 Huesken HIP2 3093 CUCCUUCAUAUGGUGUGUCug GACACACCAUAUGAAGGAG -2.4 -2.1 -0.5 0 1 2 -37.4 63.1 7.7 3 II 47.4 51.3 64.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1299 NM_005339 Huesken HIP2 3093 UCCUUCAUAUGGUGUGUCUgg AGACACACCAUAUGAAGGA -2.1 -2.4 -0.5 -1 0 2 -37.4 78.1 -4 7 II 42.1 53.3 81 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1300 NM_005339 Huesken HIP2 3093 CCUUCAUAUGGUGUGUCUGga CAGACACACCAUAUGAAGG -2.1 -3.3 0.6 0 1 2 -37.1 68 3.4 3 II 47.4 44.8 72.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1301 NM_005339 Huesken HIP2 3093 UUCAUAUGGUGUGUCUGGAgg UCCAGACACACCAUAUGAA -2.4 -0.9 1.8 2 2 2 -37.4 74.8 1.6 7 II 42.1 56.9 73.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1302 NM_005339 Huesken HIP2 3093 CAUAUGGUGUGUCUGGAGGuc CCUCCAGACACACCAUAUG -3.3 -2.1 2.9 0 2 2 -39.5 68.4 5.8 5 II 52.6 51.9 66.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1303 NM_005339 Huesken HIP2 3093 UGGUGUGUCUGGAGGUCCUgc AGGACCUCCAGACACACCA -2.1 -2.1 -1.7 0 1 2 -43.9 53.7 -6.6 3 II 57.9 52.9 74.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1304 NM_005339 Huesken HIP2 3093 UGUCUGGAGGUCCUGCUAUuu AUAGCAGGACCUCCAGACA -1.1 -2.1 -1.7 2 1 2 -42 57.5 -1.6 6 II 52.6 52.9 69.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1305 NM_005339 Huesken HIP2 3093 GUCUGGAGGUCCUGCUAUUuc AAUAGCAGGACCUCCAGAC -0.9 -2.2 -1.7 0 -2 2 -40.8 46.3 -8.7 2 III 52.6 33.2 56.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1306 NM_005339 Huesken HIP2 3093 UCUGGAGGUCCUGCUAUUUcu AAAUAGCAGGACCUCCAGA -0.9 -2.4 -1.7 0 0 2 -39.5 55.3 -3.3 5 II 47.4 50.6 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1307 NM_005339 Huesken HIP2 3093 AGGUCCUGCUAUUUCUCCUcu AGGAGAAAUAGCAGGACCU -2.1 -2.1 0.8 3 2 2 -39.5 80.7 3.7 4 II 47.4 53.8 69.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1308 NM_005339 Huesken HIP2 3093 GGUCCUGCUAUUUCUCCUCuu GAGGAGAAAUAGCAGGACC -2.4 -3.3 2.2 1 1 2 -39.8 65.4 10.4 3 II 52.6 48.7 54.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1309 NM_005339 Huesken HIP2 3093 CUAUUUCUCCUCUUAAUUCug GAAUUAAGAGGAGAAAUAG -2.4 -2.1 3.1 0 1 2 -30.6 90.6 5.4 5 II 31.6 62.5 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1310 NM_005339 Huesken HIP2 3093 UCCUCUUAAUUCUGUAAAAuu UUUUACAGAAUUAAGAGGA -0.9 -2.4 0.8 0 -2 2 -30.2 83 -6.1 5 II 26.3 48.2 47.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1311 NM_005339 Huesken HIP2 3093 UGUAAAAUUCUCAUCUACAag UGUAGAUGAGAAUUUUACA -2.1 -2.1 -2.3 0 1 1 -30.5 82.5 -3.7 6 II 26.3 65.6 89.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1312 NM_005339 Huesken HIP2 3093 GUAAAAUUCUCAUCUACAAga UUGUAGAUGAGAAUUUUAC -0.9 -2.2 -0.6 2 -1 1 -29.3 75.6 -3.4 5 II 26.3 43.1 55.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1313 NM_005339 Huesken HIP2 3093 UAAAAUUCUCAUCUACAAGau CUUGUAGAUGAGAAUUUUA -2.1 -1.3 0.2 1 4 1 -29.2 98.2 12.8 8 Ia 26.3 76.4 91.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1314 NM_005339 Huesken HIP2 3093 AAAAUUCUCAUCUACAAGAuc UCUUGUAGAUGAGAAUUUU -2.4 -0.9 -1.4 2 1 1 -30.3 87.4 -6.1 6 II 26.3 66.5 84.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1315 NM_005339 Huesken HIP2 3093 AAAUUCUCAUCUACAAGAUcu AUCUUGUAGAUGAGAAUUU -1.1 -0.9 -1.7 2 2 1 -30.5 85.6 -5.9 6 II 26.3 56.4 81.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1316 NM_005339 Huesken HIP2 3093 UUCUCAUCUACAAGAUCUAcu UAGAUCUUGUAGAUGAGAA -1.3 -0.9 -1.7 0 0 1 -33.4 74.3 -8.7 6 II 31.6 58.1 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1317 NM_005339 Huesken HIP2 3093 CUCAUCUACAAGAUCUACUuu AGUAGAUCUUGUAGAUGAG -2.1 -2.1 -0.2 1 -1 1 -34.4 83.5 -3.9 5 II 36.8 58.6 88.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1318 NM_005339 Huesken HIP2 3093 UCAUCUACAAGAUCUACUUua AAGUAGAUCUUGUAGAUGA -0.9 -2.4 -0.2 0 1 1 -33.2 87.7 -4 7 II 31.6 65.7 88.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1319 NM_005339 Huesken HIP2 3093 CUACAAGAUCUACUUUAAUuu AUUAAAGUAGAUCUUGUAG -1.1 -2.1 0.6 0 -1 1 -29.4 66.1 1.5 4 II 26.3 44.3 45.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1320 NM_053656 Huesken P2rx2 22953 GGUCUUUGUCCCAUAUGCUgg AGCAUAUGGGACAAAGACC -2.1 -3.3 -0.1 2 1 3 -38.3 60.9 -8.9 3 II 47.4 42.5 53.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1321 NM_053656 Huesken P2rx2 22953 GUCUUUGUCCCAUAUGCUGgc CAGCAUAUGGGACAAAGAC -2.1 -2.2 1.1 1 1 3 -37.1 68.3 -2.4 4 II 47.4 50.7 51.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1322 NM_053656 Huesken P2rx2 22953 GUCCCAUAUGCUGGCCAAGug CUUGGCCAGCAUAUGGGAC -2.1 -2.2 -2.4 1 0 4 -41.6 43.4 0.7 0 II 57.9 36.7 52 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1323 NM_053656 Huesken P2rx2 22953 GCCAAGUGUGUCCACCACCug GGUGGUGGACACACUUGGC -3.3 -3.4 -3 1 0 3 -43.5 41.2 10.2 1 II 63.2 49.1 52.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1324 NM_053656 Huesken P2rx2 22953 ACCACCUGCUCAGUCAGAGca CUCUGACUGAGCAGGUGGU -2.1 -2.2 -1.8 3 3 2 -42.7 53.7 0 2 II 57.9 47.3 46.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1325 NM_053656 Huesken P2rx2 22953 CUCAGUCAGAGCAGAGAUGga CAUCUCUGCUCUGACUGAG -2.1 -2.1 -1.1 -1 -1 2 -39.7 47.9 -6.9 2 II 52.6 44.8 42.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1326 NM_053656 Huesken P2rx2 22953 CGAGGAGACUGGACAGCCAgu UGGCUGUCCAGUCUCCUCG -2.1 -2.4 -2.9 0 -2 3 -44.4 25.5 -8.3 0 III 63.2 32.1 67.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1327 NM_053656 Huesken P2rx2 22953 UGAUGGAGGGCUGGGUGGCug GCCACCCAGCCCUCCAUCA -3.4 -2.1 0.2 0 4 4 -47.3 38.9 8.1 5 Ib 68.4 56.6 60.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1328 NM_053656 Huesken P2rx2 22953 UGGAGGGCUGGGUGGCUGAuc UCAGCCACCCAGCCCUCCA -2.4 -2.1 0 -1 -1 4 -48.3 38.3 -3.8 5 II 68.4 45.2 51.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1329 NM_053656 Huesken P2rx2 22953 GGUGGCUGAUCCUGGGAGUag ACUCCCAGGAUCAGCCACC -2.2 -3.3 -0.9 0 -1 3 -45.2 38.2 -8.7 1 III 63.2 27.5 44.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1330 NM_053656 Huesken P2rx2 22953 GCUGAUCCUGGGAGUAGUGac CACUACUCCCAGGAUCAGC -2.1 -3.4 0.1 -1 1 3 -42 39.4 0.1 1 II 57.9 34.6 46.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1331 NM_053656 Huesken P2rx2 22953 GAUCCUGGGAGUAGUGACUag AGUCACUACUCCCAGGAUC -2.1 -2.4 0.1 1 0 3 -41.1 55.1 -3.5 4 III 52.6 41.7 64.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1332 NM_053656 Huesken P2rx2 22953 CUGGCCCAAGACAAGGGCAag UGCCCUUGUCUUGGGCCAG -2.1 -2.1 -6.9 -1 -2 5 -44.4 37.3 -8.4 -1 III 63.2 37.2 37 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1333 NM_053656 Huesken P2rx2 22953 AAGACAAGGGCAAGGGUCAca UGACCCUUGCCCUUGUCUU -2.1 -0.9 -0.1 1 0 4 -41.1 44.9 -8.7 6 II 52.6 48.6 53.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1334 NM_053656 Huesken P2rx2 22953 UCACAGGCCAUCUACUUGAgg UCAAGUAGAUGGCCUGUGA -2.4 -2.4 0.7 2 0 4 -39.6 58.5 -3.4 8 II 47.4 60.3 67.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1335 NM_053656 Huesken P2rx2 22953 UUGUCGAACUUCUUAUGGCug GCCAUAAGAAGUUCGACAA -3.4 -0.9 1.6 1 5 3 -35.1 81 7.4 6 Ib 42.1 73.9 88.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1336 NM_053656 Huesken P2rx2 22953 UAUGGCUGUAGAGCUUGUUuu AACAAGCUCUACAGCCAUA -0.9 -1.3 -1 1 2 3 -37.1 69.6 -4 6 II 42.1 61.8 76.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1337 NM_053656 Huesken P2rx2 22953 CCAGUCACACAGGAAGGAGcc CUCCUUCCUGUGUGACUGG -2.1 -3.3 1 -1 0 2 -41.4 39.3 0.3 2 II 57.9 38.8 47.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1338 NM_053656 Huesken P2rx2 22953 GGAGCCCACCCCGAUGGAGgu CUCCAUCGGGGUGGGCUCC -2.1 -3.3 -4.5 1 1 5 -47.8 25.2 -4.7 -1 II 73.7 27.9 38.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1339 NM_053656 Huesken P2rx2 22953 GAGGUCAGAGCAGUGGCCAga UGGCCACUGCUCUGACCUC -2.1 -2.4 -0.5 0 0 4 -45.1 37.2 -3.8 2 III 63.2 38 57 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1340 NM_053656 Huesken P2rx2 22953 GCAGUGGCCAGAUUGAUGAug UCAUCAAUCUGGCCACUGC -2.4 -3.4 1.4 1 -1 4 -40.6 53.6 -1.4 5 III 52.6 39.7 43.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1341 NM_053656 Huesken P2rx2 22953 GGGAAUGAGACUGAAUUUCcc GAAAUUCAGUCUCAUUCCC -2.4 -3.3 1.8 1 -1 3 -35 59.9 10.8 5 II 42.1 47.2 39.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1342 NM_053656 Huesken P2rx2 22953 GAAUGAGACUGAAUUUCCCug GGGAAAUUCAGUCUCAUUC -3.3 -2.4 -2.1 1 4 3 -35 64 7.1 3 II 42.1 54.3 72.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1343 NM_053656 Huesken P2rx2 22953 GAGACUGAAUUUCCCUGCCug GGCAGGGAAAUUCAGUCUC -3.3 -2.4 -0.6 0 2 3 -39.4 63.9 12.8 3 II 52.6 52.5 51.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1344 NM_053656 Huesken P2rx2 22953 CCAUGCACGAUAACAUCGAuu UCGAUGUUAUCGUGCAUGG -2.4 -3.3 -1.7 0 -2 2 -37 46.3 -8.3 3 III 47.4 40.8 57.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1345 NM_053656 Huesken P2rx2 22953 AUUCGAAUCCCAUAGGCUUug AAGCCUAUGGGAUUCGAAU -0.9 -1.1 -0.8 3 2 3 -36.5 61.9 -6.3 5 II 42.1 55.8 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1346 NM_053656 Huesken P2rx2 22953 GAUGAGAGUUCGAGUGGUGgu CACCACUCGAACUCUCAUC -2.1 -2.4 0.7 -1 2 2 -38.9 40.9 -2.2 4 II 52.6 41.4 64.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1347 NM_053656 Huesken P2rx2 22953 GAGUUCGAGUGGUGGUAGUgc ACUACCACCACUCGAACUC -2.2 -2.4 0 -1 2 -39.9 53.8 -4 4 III 52.6 32.9 43.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1348 NM_053656 Huesken P2rx2 22953 GUAGUGCCGUUUAUCUUGUaa ACAAGAUAAACGGCACUAC -2.2 -2.2 2.8 1 1 4 -35.1 63.2 -1.2 4 III 42.1 46.1 50.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1349 NM_053656 Huesken P2rx2 22953 UAUCUUGUAAUACUUGGCAaa UGCCAAGUAUUACAAGAUA -2.1 -1.3 1.7 1 3 3 -32.8 86.5 1 8 II 31.6 69.4 76.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1350 NM_053656 Huesken P2rx2 22953 AUCUUGUAAUACUUGGCAAac UUGCCAAGUAUUACAAGAU -0.9 -1.1 1.8 2 1 3 -32.4 84.6 -1.5 6 II 31.6 50.6 56.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1351 NM_053656 Huesken P2rx2 22953 GGCAAACCUGAAGUUGUAGcc CUACAACUUCAGGUUUGCC -2.1 -3.3 -0.1 0 0 3 -36.5 53.5 7.3 3 II 47.4 33.1 57 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1352 NM_053656 Huesken P2rx2 22953 AGCCUGAGGAGGCAGGGUCau GACCCUGCCUCCUCAGGCU -2.4 -2.1 -4.5 3 2 3 -47.4 40.5 9.8 3 II 68.4 50.5 61.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1353 NM_053656 Huesken P2rx2 22953 UUGCACUCUGAUUCAGACAag UGUCUGAAUCAGAGUGCAA -2.1 -0.9 -1.4 2 0 2 -37.1 76.6 4.3 5 II 42.1 64.5 80.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1354 NM_053656 Huesken P2rx2 22953 ACAAGUCCAGGUCACAGUUcc AACUGUGACCUGGACUUGU -0.9 -2.2 1.5 1 1 2 -38.9 58.1 1.5 4 II 47.4 48.2 38.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1355 NM_053656 Huesken P2rx2 22953 GUCCAGGUCACAGUUCCAGuu CUGGAACUGUGACCUGGAC -2.1 -2.2 -0.1 2 2 2 -41.5 45.4 2.7 3 II 57.9 43.9 70.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1356 NM_053656 Huesken P2rx2 22953 GUUCCAGUUGAUGAUGACUcc AGUCAUCAUCAACUGGAAC -2.1 -2.2 0.9 1 0 2 -36.1 63.3 1.4 3 III 42.1 44.9 33.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1357 NM_053656 Huesken P2rx2 22953 AUGAUGACUCCAAUGACACcg GUGUCAUUGGAGUCAUCAU -2.2 -1.1 0.4 1 4 2 -36.3 69.5 4.8 6 Ia 42.1 67.3 59 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1358 NM_053656 Huesken P2rx2 22953 GUUCUGUGAAGUUCUCUCCug GGAGAGAACUUCACAGAAC -3.3 -2.2 -2.1 2 2 2 -37.2 79.8 10.4 5 II 47.4 60.2 61.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1359 NM_053656 Huesken P2rx2 22953 GUUCUCUCCUGCCUUCUCAac UGAGAAGGCAGGAGAGAAC -2.1 -2.2 1.7 3 0 3 -40.7 68.7 -1.4 5 II 52.6 43.2 32.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1360 NM_053656 Huesken P2rx2 22953 UCCUGCCUUCUCAACAAUGaa CAUUGUUGAGAAGGCAGGA -2.1 -2.4 -1.5 0 1 3 -37.9 61.6 -4.9 3 II 47.4 60.1 61.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1361 NM_053656 Huesken P2rx2 22953 CAACAAUGAAACCCAGCCUga AGGCUGGGUUUCAUUGUUG -2.1 -2.1 1.1 1 0 3 -37.4 56.4 -0.9 5 II 47.4 50.6 64.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1362 NM_053656 Huesken P2rx2 22953 AUGGGUCAGAGUCCUGAUCaa GAUCAGGACUCUGACCCAU -2.4 -1.1 -2.5 2 2 3 -41.1 62.4 12.8 3 II 52.6 58.9 81.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1363 NM_053656 Huesken P2rx2 22953 AUGUGCAAUGCUUGAGGUAgu UACCUCAAGCAUUGCACAU -1.3 -1.1 0.4 0 0 2 -36.9 59.9 -3.1 5 II 42.1 46 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1364 NM_053656 Huesken P2rx2 22953 UCACUCUUCUGGCUUGCAAug UUGCAAGCCAGAAGAGUGA -0.9 -2.4 1.7 3 1 3 -39 69.8 1 6 II 47.4 49 72.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1365 NM_053656 Huesken P2rx2 22953 GAACUUGAACUUGGGGUAGug CUACCCCAAGUUCAAGUUC -2.1 -2.4 2.2 0 1 4 -36.7 53.7 3 5 II 47.4 42.7 62.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1366 NM_053656 Huesken P2rx2 22953 UGGAUGCUGUUCUUGAUGAgg UCAUCAAGAACAGCAUCCA -2.4 -2.1 1.4 1 0 2 -37.2 73 -3.8 6 II 42.1 54.6 53.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1367 NM_053656 Huesken P2rx2 22953 GAUGAGGAUGGUGAAAUUUgg AAAUUUCACCAUCCUCAUC -0.9 -2.4 4.3 0 -1 2 -33.7 57.3 1.8 5 III 36.8 43.4 23.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1368 NM_053656 Huesken P2rx2 22953 CCCAGAAAAUGGUUGUCAGaa CUGACAACCAUUUUCUGGG -2.1 -3.3 -1.9 -1 0 3 -36.4 58.2 0.3 1 II 47.4 36.8 40.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1369 NM_053656 Huesken P2rx2 22953 GAAAAUGGUUGUCAGAAGUuc ACUUCUGACAACCAUUUUC -2.2 -2.4 1.8 0 0 2 -33.2 68 4.2 5 II 36.8 47.6 33.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1370 NM_053656 Huesken P2rx2 22953 GUUCCAUCCUCCACCGGGCac GCCCGGUGGAGGAUGGAAC -3.4 -2.2 -1.5 3 3 6 -45.5 45.8 0.1 1 II 68.4 47.4 48.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1371 NM_053656 Huesken P2rx2 22953 GACACCUCGCAGGUCUUGGag CCAAGACCUGCGAGGUGUC -3.3 -2.4 -2.2 2 2 3 -43 59.2 4.6 2 II 63.2 45.9 68.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1372 NM_053656 Huesken P2rx2 22953 AUAGGGUACACAGUGCCCUgu AGGGCACUGUGUACCCUAU -2.1 -1.1 -3.6 3 4 4 -41.7 52.9 -4 5 II 52.6 64.9 55 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1373 NM_053656 Huesken P2rx2 22953 AGUGCCCUGUGCGAAUCCCau GGGAUUCGCACAGGGCACU -3.3 -2.1 -1.2 2 4 4 -44.1 47 5.1 1 II 63.2 50.1 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1374 NM_053656 Huesken P2rx2 22953 UGCGAAUCCCAUUGCCUUGca CAAGGCAAUGGGAUUCGCA -2.1 -2.1 -0.1 1 1 3 -39.3 65.1 8 6 Ib 52.6 58.8 64.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1375 NM_053656 Huesken P2rx2 22953 CAUUGCCUUGCAUGUCCAGcu CUGGACAUGCAAGGCAAUG -2.1 -2.1 -0.4 -2 1 3 -38.8 55 -4.4 3 II 52.6 40.3 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1376 NM_053656 Huesken P2rx2 22953 CCUUGCAUGUCCAGCUGUCcg GACAGCUGGACAUGCAAGG -2.4 -3.3 -1.4 -1 0 2 -41.4 45.4 -1.9 1 II 57.9 39.6 35.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1377 NM_053656 Huesken P2rx2 22953 UCUGAAUGGCAGGUAGAGCug GCUCUACCUGCCAUUCAGA -3.4 -2.4 -0.5 2 4 3 -40.8 56.3 14.7 6 Ia 52.6 61.1 79.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1378 NM_053656 Huesken P2rx2 22953 GAAUGGCAGGUAGAGCUGUga ACAGCUCUACCUGCCAUUC -2.2 -2.4 -0.5 1 0 3 -40.6 38.2 -4 4 III 52.6 40 42.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1379 NM_053656 Huesken P2rx2 22953 UGGCAGGUAGAGCUGUGAAcc UUCACAGCUCUACCUGCCA -0.9 -2.1 -0.5 1 0 3 -41.6 53.3 6 5 II 52.6 43.4 51.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1380 NM_053656 Huesken P2rx2 22953 AUGUUCCCAAGGUCUGGGAag UCCCAGACCUUGGGAACAU -2.4 -1.1 -5.8 1 1 3 -41.5 66.3 -3.8 5 II 52.6 47 50.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1381 NM_053656 Huesken P2rx2 22953 AAGGGGUAACCUCGAUCCUgg AGGAUCGAGGUUACCCCUU -2.1 -0.9 -1.9 1 2 4 -41 49 -0.9 3 II 52.6 50.9 76.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1382 NM_053656 Huesken P2rx2 22953 UCGAUCCUGGUGAUGAUGCug GCAUCAUCACCAGGAUCGA -3.4 -2.4 0.8 1 3 2 -40.4 67.4 7.1 6 II 52.6 66.1 78.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1383 NM_053656 Huesken P2rx2 22953 GAUGAUGCUGACUACACUGcc CAGUGUAGUCAGCAUCAUC -2.1 -2.4 -0.8 0 2 2 -37.5 62.3 2.7 4 II 47.4 55.5 78.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1384 NM_053656 Huesken P2rx2 22953 GGGGCUUUACGUAUUCCUCca GAGGAAUACGUAAAGCCCC -2.4 -3.3 0.9 1 1 5 -38.8 66 10.2 1 II 52.6 46.4 34.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1385 NM_053656 Huesken P2rx2 22953 GUCCCACACUUUGUCUUCCga GGAAGACAAAGUGUGGGAC -3.3 -2.2 1 2 2 3 -39.1 59.9 12.8 2 II 52.6 46.2 69.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1386 NM_053656 Huesken P2rx2 22953 UCCCACACUUUGUCUUCCGac CGGAAGACAAAGUGUGGGA -2.4 -2.4 1 1 3 3 -39.3 63 2.7 5 II 52.6 62.8 64.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1387 NM_053656 Huesken P2rx2 22953 UGGUGAUCCCCUUGACUUUgg AAAGUCAAGGGGAUCACCA -0.9 -2.1 -2.2 1 -1 4 -39.1 65.1 -3.3 5 II 47.4 50.8 66.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1388 NM_053656 Huesken P2rx2 22953 CUUGACUUUGGUGAUGAUGga CAUCAUCACCAAAGUCAAG -2.1 -2.1 2.5 0 0 2 -34.5 69.7 3.7 4 II 42.1 54.6 71.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1389 NM_053656 Huesken P2rx2 22953 UGAUGAUGGAGCUCUCCGGuc CCGGAGAGCUCCAUCAUCA -3.3 -2.1 -3.3 2 4 4 -42.5 62.7 -2.4 5 Ia 57.9 65.6 54.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1390 NM_053656 Huesken P2rx2 22953 CCGGUCUCGCUGUCCUGGUag ACCAGGACAGCGAGACCGG -2.2 -3.3 0.1 1 -2 4 -45.7 40.2 -6 1 III 68.4 36.1 49.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1391 NM_053656 Huesken P2rx2 22953 GUCUCGCUGUCCUGGUAGCuu GCUACCAGGACAGCGAGAC -3.4 -2.2 -1.9 0 1 3 -43.5 49.9 2.7 0 II 63.2 37.1 60.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1392 NM_053656 Huesken P2rx2 22953 CUGGUAGCUUUUCUGCACGau CGUGCAGAAAAGCUACCAG -2.4 -2.1 -0.7 -1 1 2 -38 59.3 5.8 3 II 52.6 54.8 80.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1393 NM_053656 Huesken P2rx2 22953 UGGUAGCUUUUCUGCACGAug UCGUGCAGAAAAGCUACCA -2.4 -2.1 -0.7 -1 0 2 -38.3 56.1 -3.4 5 II 47.4 48.7 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1394 NM_053656 Huesken P2rx2 22953 UUCUGCACGAUGAAGACGUac ACGUCUUCAUCGUGCAGAA -2.2 -0.9 -0.4 1 2 2 -37.8 64.8 -6.6 7 II 47.4 68 85.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1395 NM_053656 Huesken P2rx2 22953 GAAGUAAAGCAGGAUGAGAag UCUCAUCCUGCUUUACUUC -2.4 -2.4 3.3 1 -1 2 -36.2 48.8 -1.5 4 II 42.1 38.9 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1396 NM_053656 Huesken P2rx2 22953 CAGGCGCCGAUUCCGCACCac GGUGCGGAAUCGGCGCCUG -3.3 -2.1 -7.5 0 0 7 -45.9 41.4 10.8 0 II 73.7 50.6 69.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1397 NM_003348 Huesken UBE2N 7334 UAGCCUAGUCCAUGCUCUAgc UAGAGCAUGGACUAGGCUA -1.3 -1.3 -1.1 0 0 3 -40.1 59.2 -6.1 4 II 47.4 54.3 73.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1398 NM_003348 Huesken UBE2N 7334 UCCAUGCUCUAGCUGUUUCua GAAACAGCUAGAGCAUGGA -2.4 -2.4 -1.4 1 2 2 -38.4 77.8 14.4 5 II 47.4 59.8 100.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1399 NM_003348 Huesken UBE2N 7334 AUGCUCUAGCUGUUUCUAUgg AUAGAAACAGCUAGAGCAU -1.1 -1.1 -1.4 4 1 2 -35.1 78 -1.6 5 II 36.8 54.8 91.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1400 NM_003348 Huesken UBE2N 7334 UGCUCUAGCUGUUUCUAUGgc CAUAGAAACAGCUAGAGCA -2.1 -2.1 -1.4 1 2 2 -36.1 90 5.4 4 Ib 42.1 63.6 95.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1401 NM_003348 Huesken UBE2N 7334 CUAGCUGUUUCUAUGGCUUgg AAGCCAUAGAAACAGCUAG -0.9 -2.1 -0.5 -1 0 3 -35.8 67.6 -5.6 3 III 42.1 49.3 90.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1402 NM_003348 Huesken UBE2N 7334 GCUGUUUCUAUGGCUUGGGcu CCCAAGCCAUAGAAACAGC -3.3 -3.4 1.9 1 2 3 -39 58.8 0 4 II 52.6 48.5 60.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1403 NM_003348 Huesken UBE2N 7334 UGUUUCUAUGGCUUGGGCUuc AGCCCAAGCCAUAGAAACA -2.1 -2.1 0.2 1 3 4 -39 82.5 -4 7 II 47.4 63.3 91.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1404 NM_003348 Huesken UBE2N 7334 GUUUCUAUGGCUUGGGCUUcg AAGCCCAAGCCAUAGAAAC -0.9 -2.2 0.2 0 0 4 -37.8 68.4 -3.3 4 II 47.4 42 61.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1405 NM_003348 Huesken UBE2N 7334 UUUCUAUGGCUUGGGCUUCgu GAAGCCCAAGCCAUAGAAA -2.4 -0.9 0.2 2 3 4 -38 66.6 10.4 8 Ia 47.4 66.9 90.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1406 NM_003348 Huesken UBE2N 7334 UUCUAUGGCUUGGGCUUCGuu CGAAGCCCAAGCCAUAGAA -2.4 -0.9 0.2 0 3 4 -39.5 61.8 2.7 8 Ia 52.6 66.8 84.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1407 NM_003348 Huesken UBE2N 7334 UCUAUGGCUUGGGCUUCGUug ACGAAGCCCAAGCCAUAGA -2.2 -2.4 0.2 0 2 4 -40.8 58.8 -4 7 II 52.6 53.5 77.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1408 NM_003348 Huesken UBE2N 7334 UAUGGCUUGGGCUUCGUUGgu CAACGAAGCCCAAGCCAUA -2.1 -1.3 0.2 2 4 4 -39.3 77.3 0 7 Ib 52.6 71.1 94 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1409 NM_003348 Huesken UBE2N 7334 UUGGGCUUCGUUGGUCUUCca GAAGACCAACGAAGCCCAA -2.4 -0.9 1 2 4 -39.3 64.1 10.4 6 II 52.6 68.5 85.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1410 NM_003348 Huesken UBE2N 7334 CUUCGUUGGUCUUCCACUGcu CAGUGGAAGACCAACGAAG -2.1 -2.1 -1.4 2 1 2 -38.1 63.6 -1.3 2 II 52.6 53.6 78 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1411 NM_003348 Huesken UBE2N 7334 GGUCUUCCACUGCUCCGCUac AGCGGAGCAGUGGAAGACC -2.1 -3.3 0.2 1 1 4 -44.2 46.7 0.8 1 III 63.2 35.3 43.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1412 NM_003348 Huesken UBE2N 7334 GUCUUCCACUGCUCCGCUAca UAGCGGAGCAGUGGAAGAC -1.3 -2.2 0.2 1 -2 4 -42.2 54.5 -6.1 2 III 57.9 30.4 40.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1413 NM_003348 Huesken UBE2N 7334 CUGCUCCGCUACAUCAUUUgc AAAUGAUGUAGCGGAGCAG -0.9 -2.1 -0.3 1 -2 4 -37.4 61.8 -6.3 3 III 47.4 43.4 43.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1414 NM_003348 Huesken UBE2N 7334 UGCUCCGCUACAUCAUUUGcu CAAAUGAUGUAGCGGAGCA -2.1 -2.1 0.4 0 1 4 -37.4 75.3 -2.4 7 II 47.4 61.3 64.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1415 NM_003348 Huesken UBE2N 7334 GCUCCGCUACAUCAUUUGCua GCAAAUGAUGUAGCGGAGC -3.4 -3.4 -0.1 1 1 4 -38.7 61.4 15.1 2 II 52.6 39 49.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1416 NM_003348 Huesken UBE2N 7334 CGCUACAUCAUUUGCUAAUgg AUUAGCAAAUGAUGUAGCG -1.1 -2.4 -0.3 -1 -4 3 -32.9 72.4 -0.3 4 III 36.8 37.7 34.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1417 NM_003348 Huesken UBE2N 7334 GCUACAUCAUUUGCUAAUGga CAUUAGCAAAUGAUGUAGC -2.1 -3.4 -1.6 1 0 2 -32.6 70.6 3 2 II 36.8 43.7 30.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1418 NM_003348 Huesken UBE2N 7334 CUACAUCAUUUGCUAAUGGau CCAUUAGCAAAUGAUGUAG -3.3 -2.1 -1.9 0 2 2 -32.5 67.9 5.4 3 II 36.8 55.3 77.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1419 NM_003348 Huesken UBE2N 7334 CAUCAUUUGCUAAUGGAUCau GAUCCAUUAGCAAAUGAUG -2.4 -2.1 -1.3 2 1 2 -32.8 73.4 7.8 3 II 36.8 59.9 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1420 NM_003348 Huesken UBE2N 7334 AUCAUUUGCUAAUGGAUCAuc UGAUCCAUUAGCAAAUGAU -2.1 -1.1 -0.4 2 0 2 -32.8 84.2 -1.5 7 II 31.6 59 70.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1421 NM_003348 Huesken UBE2N 7334 UGCUAAUGGAUCAUCUGGAuu UCCAGAUGAUCCAUUAGCA -2.4 -2.1 0.7 2 1 2 -37.7 67 -3.7 7 II 42.1 56.3 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1422 NM_003348 Huesken UBE2N 7334 UGGAUCAUCUGGAUUGGGAgc UCCCAAUCCAGAUGAUCCA -2.4 -2.1 1.4 1 1 3 -39.9 69.5 -4 6 II 47.4 53.9 78.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1423 NM_003348 Huesken UBE2N 7334 GGAUCAUCUGGAUUGGGAGca CUCCCAAUCCAGAUGAUCC -2.1 -3.3 1.4 1 2 3 -39.9 61.5 2.3 3 II 52.6 39.9 58.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1424 NM_003348 Huesken UBE2N 7334 GAUAGCAGAACUGUGCGGAuc UCCGCACAGUUCUGCUAUC -2.4 -2.4 -1.8 0 1 4 -40 55.3 -0.8 4 II 52.6 39.6 63.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1425 NM_003348 Huesken UBE2N 7334 AUAGCAGAACUGUGCGGAUcu AUCCGCACAGUUCUGCUAU -1.1 -1.1 -1.8 0 2 4 -38.7 48.9 -4 4 II 47.4 45.3 54.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1426 NM_003348 Huesken UBE2N 7334 CAGAACUGUGCGGAUCUGCag GCAGAUCCGCACAGUUCUG -3.4 -2.1 -1.4 0 0 4 -40.8 51.3 5.8 3 II 57.9 53.4 86.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1427 NM_003348 Huesken UBE2N 7334 AUCUGCAGUGCUGGGGACCac GGUCCCCAGCACUGCAGAU -3.3 -1.1 0.4 0 3 4 -45 48.9 8.1 4 Ib 63.2 57.1 62.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1428 NM_003348 Huesken UBE2N 7334 CUGCAGUGCUGGGGACCACuu GUGGUCCCCAGCACUGCAG -2.2 -2.1 -2.4 1 0 4 -45.8 28.5 8.1 1 II 68.4 38.6 59.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1429 NM_003348 Huesken UBE2N 7334 GCAGUGCUGGGGACCACUUau AAGUGGUCCCCAGCACUGC -0.9 -3.4 -2.7 1 -1 4 -44.6 33.2 -6.6 0 III 63.2 33.1 48.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1430 NM_003348 Huesken UBE2N 7334 GGGGACCACUUAUCUUUCAaa UGAAAGAUAAGUGGUCCCC -2.1 -3.3 0.2 1 -3 4 -38.3 50.6 -1.1 2 III 47.4 30.6 34.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1431 NM_003348 Huesken UBE2N 7334 GACCACUUAUCUUUCAAAAua UUUUGAAAGAUAAGUGGUC -0.9 -2.4 1 2 -2 2 -31.1 79 2 3 III 31.6 36.1 35.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1432 NM_003348 Huesken UBE2N 7334 CUUAUCUUUCAAAAUAUCUag AGAUAUUUUGAAAGAUAAG -2.1 -2.1 0.4 0 -1 1 -26.9 93.9 -6.3 6 II 21.1 62.7 57.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1433 NM_003348 Huesken UBE2N 7334 UUAUCUUUCAAAAUAUCUAga UAGAUAUUUUGAAAGAUAA -1.3 -0.9 0.4 2 2 1 -26.1 105.8 -1.7 8 II 15.8 75.2 80.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1434 NM_003348 Huesken UBE2N 7334 UAUCUUUCAAAAUAUCUAGac CUAGAUAUUUUGAAAGAUA -2.1 -1.3 1.2 2 3 1 -27.3 105.7 2.3 9 Ia 21.1 78.9 85.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1435 NM_003348 Huesken UBE2N 7334 UUUCAAAAUAUCUAGACAUau AUGUCUAGAUAUUUUGAAA -1.1 -0.9 1.3 1 2 1 -28.2 85.2 -3.6 8 II 21.1 70.6 75.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1436 NM_003348 Huesken UBE2N 7334 CUAGACAUAUUCUUCCCAAcu UUGGGAAGAAUAUGUCUAG -0.9 -2.1 -1.2 -1 -1 3 -34 66.1 -3.1 3 II 36.8 45.1 52.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1437 NM_003348 Huesken UBE2N 7334 UUCUUCCCAACUUGUCUACau GUAGACAAGUUGGGAAGAA -2.2 -0.9 2 -1 2 3 -35.8 86.6 8.1 8 Ib 42.1 62.4 94 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1438 NM_003348 Huesken UBE2N 7334 UUCCCAACUUGUCUACAUUag AAUGUAGACAAGUUGGGAA -0.9 -0.9 1 1 1 3 -34.5 78.5 3.8 5 II 36.8 58.3 93.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1439 NM_003348 Huesken UBE2N 7334 CCAACUUGUCUACAUUAGGau CCUAAUGUAGACAAGUUGG -3.3 -3.3 -0.9 0 0 2 -34.6 65 0.4 3 II 42.1 53.2 69.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1440 NM_003348 Huesken UBE2N 7334 UUGUCUACAUUAGGAUGAUaa AUCAUCCUAAUGUAGACAA -1.1 -0.9 1 -1 1 2 -33.1 71.2 -4 6 II 31.6 55.2 46.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1441 NM_003348 Huesken UBE2N 7334 CUACAUUAGGAUGAUAAAUuu AUUUAUCAUCCUAAUGUAG -1.1 -2.1 1.5 2 -2 2 -29.7 73.6 2.1 4 II 26.3 50.3 49.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1442 NM_003348 Huesken UBE2N 7334 UAGGAUGAUAAAUUUUGGUca ACCAAAAUUUAUCAUCCUA -2.2 -1.3 4.1 0 3 2 -30.3 88.2 3.4 7 II 26.3 70.5 81.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1443 NM_003348 Huesken UBE2N 7334 AAAUUUUGGUCAUGAAACGua CGUUUCAUGACCAAAAUUU -2.4 -0.9 0.2 2 4 2 -29.7 80.2 -2.4 7 Ia 31.6 68.8 100 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1444 NM_003348 Huesken UBE2N 7334 AAUUUUGGUCAUGAAACGUac ACGUUUCAUGACCAAAAUU -2.2 -0.9 0.2 1 3 2 -31 79.4 1.4 7 II 31.6 61 92.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1445 NM_003348 Huesken UBE2N 7334 GUCAUGAAACGUACUUUAGgg CUAAAGUACGUUUCAUGAC -2.1 -2.2 1 0 0 2 -31.7 76 0.4 5 II 36.8 48 79.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1446 NM_003348 Huesken UBE2N 7334 UUAGGGGCUGCCAUUGGGUau ACCCAAUGGCAGCCCCUAA -2.2 -0.9 0.4 0 4 5 -43.5 48.9 -8.9 5 II 57.9 63.4 64 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1447 NM_003348 Huesken UBE2N 7334 GGCUGCCAUUGGGUAUUCUuc AGAAUACCCAAUGGCAGCC -2.1 -3.3 0.6 0 -1 3 -40.4 50.9 -1.6 2 III 52.6 27.3 44.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1448 NM_003348 Huesken UBE2N 7334 GGGUAUUCUUCUGGAAGGAau UCCUUCCAGAAGAAUACCC -2.4 -3.3 0 0 -2 3 -38.5 49.2 -0.4 3 II 47.4 28.6 36.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1449 NM_003348 Huesken UBE2N 7334 UAUUCUUCUGGAAGGAAUAgu UAUUCCUUCCAGAAGAAUA -1.3 -1.3 0 0 0 2 -33 82.6 -6.3 7 II 31.6 62.2 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1450 NM_003348 Huesken UBE2N 7334 CUUCUGGAAGGAAUAGUUCaa GAACUAUUCCUUCCAGAAG -2.4 -2.1 0.5 0 1 2 -34.9 63.4 5.1 5 II 42.1 55.3 87.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1451 NM_003348 Huesken UBE2N 7334 CUGGAAGGAAUAGUUCAAGuu CUUGAACUAUUCCUUCCAG -2.1 -2.1 1.6 -1 0 2 -34.6 52.3 3 4 II 42.1 48.8 84.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1452 NM_003348 Huesken UBE2N 7334 UGGAAGGAAUAGUUCAAGUuu ACUUGAACUAUUCCUUCCA -2.2 -2.1 1.6 0 1 2 -34.7 73.4 3.4 6 II 36.8 59.8 96.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1453 NM_003348 Huesken UBE2N 7334 GAAGGAAUAGUUCAAGUUUaa AAACUUGAACUAUUCCUUC -0.9 -2.4 2.1 0 -1 2 -31.1 63.6 1.5 4 II 31.6 46.1 43.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1454 NM_003348 Huesken UBE2N 7334 GGAAUAGUUCAAGUUUAAAag UUUAAACUUGAACUAUUCC -0.9 -3.3 2.1 0 -2 2 -28.8 69.2 0.9 4 II 26.3 32.8 29.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1455 NM_003348 Huesken UBE2N 7334 AGUUCAAGUUUAAAAGUCCcu GGACUUUUAAACUUGAACU -3.3 -2.1 1.9 1 3 2 -30.7 72.7 4.8 6 Ia 31.6 64.2 87.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1456 NM_003348 Huesken UBE2N 7334 AAAAGUCCCUCCCUCAAAGgg CUUUGAGGGAGGGACUUUU -2.1 -0.9 -0.8 2 4 3 -37.6 67.9 0 5 Ia 47.4 59.2 70.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1457 NM_003348 Huesken UBE2N 7334 GAAUCCUGAGGGCCAGCAAug UUGCUGGCCCUCAGGAUUC -0.9 -2.4 -1.3 1 -1 5 -42.7 50.3 -1.4 2 II 57.9 30.5 50.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1458 NM_003348 Huesken UBE2N 7334 GAGGGCCAGCAAUGACCACau GUGGUCAUUGCUGGCCCUC -2.2 -2.4 -4.9 0 1 5 -43.8 32.3 9.7 -1 II 63.2 33.1 54.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1459 NM_003348 Huesken UBE2N 7334 GGGCCAGCAAUGACCACAUga AUGUGGUCAUUGCUGGCCC -1.1 -3.3 -4.9 1 -2 5 -42.5 37.7 -6.6 0 III 57.9 31.3 47.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1460 NM_003348 Huesken UBE2N 7334 GCCAGCAAUGACCACAUGAaa UCAUGUGGUCAUUGCUGGC -2.4 -3.4 -0.8 0 -3 3 -40.4 47.3 -1.4 3 III 52.6 34.3 50.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1461 NM_003348 Huesken UBE2N 7334 CCAGCAAUGACCACAUGAAaa UUCAUGUGGUCAUUGCUGG -0.9 -3.3 0.6 0 -3 2 -37.9 44.5 -13 3 III 47.4 32 39.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1462 NM_003348 Huesken UBE2N 7334 CAGCAAUGACCACAUGAAAau UUUCAUGUGGUCAUUGCUG -0.9 -2.1 0.6 1 -4 2 -35.5 48.5 -3 3 II 42.1 32.7 39.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1463 NM_003348 Huesken UBE2N 7334 GCAAUGACCACAUGAAAAUaa AUUUUCAUGUGGUCAUUGC -1.1 -3.4 1 0 -2 2 -33.3 58.5 -6.3 5 II 36.8 39.2 47.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1464 NM_003348 Huesken UBE2N 7334 ACAUGAAAAUAACGGGCGUug ACGCCCGUUAUUUUCAUGU -2.2 -2.2 1.8 0 2 6 -35.1 51.1 0.7 5 II 42.1 44.2 62.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1465 NM_003348 Huesken UBE2N 7334 AUGAAAAUAACGGGCGUUGcu CAACGCCCGUUAUUUUCAU -2.1 -1.1 0 0 2 6 -33.8 62.3 0.4 8 Ia 42.1 61 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1466 NM_003348 Huesken UBE2N 7334 GGGCGUUGCUCUCAUCUGGuu CCAGAUGAGAGCAACGCCC -3.3 -3.3 1.3 3 0 5 -43.1 47.7 3.1 1 II 63.2 41 65.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1467 NM_003348 Huesken UBE2N 7334 UGCUCUCAUCUGGUUCGGCuu GCCGAACCAGAUGAGAGCA -3.4 -2.1 0.8 0 4 4 -42.2 61 9.7 3 II 57.9 57.6 82.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1468 NM_003348 Huesken UBE2N 7334 CUCUCAUCUGGUUCGGCUUug AAGCCGAACCAGAUGAGAG -0.9 -2.1 3.3 0 -2 4 -39.7 67.7 -3 3 II 52.6 42.4 88.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1469 NM_003348 Huesken UBE2N 7334 AUCUGGUUCGGCUUUGAUGcc CAUCAAAGCCGAACCAGAU -2.1 -1.1 0.9 3 3 4 -37.2 78 0 5 Ib 47.4 62.9 84.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1470 NM_003348 Huesken UBE2N 7334 UGGUUCGGCUUUGAUGCCAgg UGGCAUCAAAGCCGAACCA -2.1 -2.1 -4.5 1 0 4 -40.4 57.4 -0.7 5 II 52.6 53 81.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1471 NM_003348 Huesken UBE2N 7334 CGGCUUUGAUGCCAGGAACug GUUCCUGGCAUCAAAGCCG -2.2 -2.4 -4.5 1 -2 4 -40.4 52.2 5.5 0 II 57.9 40.4 78.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1472 NM_003348 Huesken UBE2N 7334 GCUUUGAUGCCAGGAACUGgu CAGUUCCUGGCAUCAAAGC -2.1 -3.4 0.2 0 1 3 -38.9 42.8 -2.4 4 II 52.6 38.6 61.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1473 NM_003348 Huesken UBE2N 7334 UUUGAUGCCAGGAACUGGUuc ACCAGUUCCUGGCAUCAAA -2.2 -0.9 -2.7 1 3 3 -38.9 67.3 -3.9 7 II 47.4 69.2 97.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1474 NM_003348 Huesken UBE2N 7334 UGAUGCCAGGAACUGGUUCug GAACCAGUUCCUGGCAUCA -2.4 -2.1 -2.7 1 3 3 -40.4 64.4 14.4 5 II 52.6 60.4 36 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1475 NM_003348 Huesken UBE2N 7334 GAUGCCAGGAACUGGUUCUgc AGAACCAGUUCCUGGCAUC -2.1 -2.4 -2.7 0 0 3 -40.4 61.1 -4 4 III 52.6 43.9 60.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1476 NM_003342 Huesken UBE2G1 7326 UUUUCUUACACAGCGGGCAac UGCCCGCUGUGUAAGAAAA -2.1 -0.9 0.8 2 2 6 -38 74.7 -6.1 8 II 47.4 66.8 94.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1477 NM_003342 Huesken UBE2G1 7326 CUUACACAGCGGGCAACUUuu AAGUUGCCCGCUGUGUAAG -0.9 -2.1 0.2 0 -1 6 -39 47.2 -6 3 II 52.6 36.2 79 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1478 NM_003342 Huesken UBE2G1 7326 UUACACAGCGGGCAACUUUuc AAAGUUGCCCGCUGUGUAA -0.9 -0.9 0.4 2 1 6 -37.8 61 1.1 8 II 47.4 63.3 93.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1479 NM_003342 Huesken UBE2G1 7326 GGGCAACUUUUCUUUUAAAuu UUUAAAAGAAAAGUUGCCC -0.9 -3.3 2.6 1 -3 4 -30.3 63 -1.1 1 III 31.6 24.5 43.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1480 NM_003342 Huesken UBE2G1 7326 ACUUUUCUUUUAAAUUCUCca GAGAAUUUAAAAGAAAAGU -2.4 -2.2 2.3 1 3 1 -26.2 87.1 4.8 5 Ia 21.1 62.6 56.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1481 NM_003342 Huesken UBE2G1 7326 UUUUCUUUUAAAUUCUCCAuu UGGAGAAUUUAAAAGAAAA -2.1 -0.9 2.3 1 3 2 -27.3 113.4 0.9 8 II 21.1 78.6 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1482 NM_003342 Huesken UBE2G1 7326 AAAUUCUCCAUUUCUAUCUuc AGAUAGAAAUGGAGAAUUU -2.1 -0.9 0.9 3 2 2 -30.4 103.9 -1 9 II 26.3 73.7 102 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1483 NM_003342 Huesken UBE2G1 7326 UUUCUAUCUUCCCUCCAUUcu AAUGGAGGGAAGAUAGAAA -0.9 -0.9 3.9 2 2 3 -35 81.4 -3.9 7 II 36.8 65.4 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1484 NM_003342 Huesken UBE2G1 7326 UUCCCUCCAUUCUUUCGCAgc UGCGAAAGAAUGGAGGGAA -2.1 -0.9 2.7 1 2 3 -38.4 71.6 -3.8 4 II 47.4 56.5 72.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1485 NM_003342 Huesken UBE2G1 7326 CCCUCCAUUCUUUCGCAGCau GCUGCGAAAGAAUGGAGGG -3.4 -3.3 0.8 -1 -1 3 -40.6 63.4 8.4 1 II 57.9 46.4 63.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1486 NM_003342 Huesken UBE2G1 7326 CCUCCAUUCUUUCGCAGCAuc UGCUGCGAAAGAAUGGAGG -2.1 -3.3 0.8 1 -2 3 -39.4 51.1 -0.3 2 III 52.6 34.1 34.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1487 NM_003342 Huesken UBE2G1 7326 UCUUUCGCAGCAUCAACAUua AUGUUGAUGCUGCGAAAGA -1.1 -2.4 0.6 0 1 3 -36.1 70.4 -6.3 7 II 42.1 53.7 104.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1488 NM_003342 Huesken UBE2G1 7326 CUUUCGCAGCAUCAACAUUag AAUGUUGAUGCUGCGAAAG -0.9 -2.1 0.6 0 -2 3 -34.6 64 1.8 3 III 42.1 40.8 93.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1489 NM_003342 Huesken UBE2G1 7326 CAGCAUCAACAUUAGCAGGug CCUGCUAAUGUUGAUGCUG -3.3 -2.1 -0.1 0 0 2 -36.8 62.3 6 2 II 47.4 49.7 97.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1490 NM_003342 Huesken UBE2G1 7326 AGCAUCAACAUUAGCAGGUga ACCUGCUAAUGUUGAUGCU -2.2 -2.1 -0.1 1 1 2 -36.9 64.8 -3.5 6 II 42.1 54.4 93.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1491 NM_003342 Huesken UBE2G1 7326 AACAUUAGCAGGUGAGUCUcc AGACUCACCUGCUAAUGUU -2.1 -0.9 1.3 1 1 2 -37 75.3 -4 8 II 42.1 60.1 81.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1492 NM_003342 Huesken UBE2G1 7326 GCAGGUGAGUCUCCAUUAGgg CUAAUGGAGACUCACCUGC -2.1 -3.4 0.3 1 0 2 -39.6 46.8 3.1 3 II 52.6 35.3 71.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1493 NM_003342 Huesken UBE2G1 7326 UGAGUCUCCAUUAGGGUCUgc AGACCCUAAUGGAGACUCA -2.1 -2.1 -1.1 1 1 3 -39.8 70.2 -3.5 7 II 47.4 66.6 89.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1494 NM_003342 Huesken UBE2G1 7326 AGGGUCUGCCAGCAUAGAAau UUCUAUGCUGGCAGACCCU -0.9 -2.1 0.4 3 -1 3 -41.7 53.1 1 4 II 52.6 39.6 61 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1495 NM_003342 Huesken UBE2G1 7326 CCAGCAUAGAAAUGACACUaa AGUGUCAUUUCUAUGCUGG -2.1 -3.3 0 0 -2 2 -35.9 53.3 -3.7 3 III 42.1 43.1 47.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1496 NM_003342 Huesken UBE2G1 7326 AGCAUAGAAAUGACACUAAuc UUAGUGUCAUUUCUAUGCU -0.9 -2.1 0.4 1 -2 2 -32.7 64.2 -6.3 7 II 31.6 44.3 54 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1497 NM_003342 Huesken UBE2G1 7326 AUAGAAAUGACACUAAUCAug UGAUUAGUGUCAUUUCUAU -2.1 -1.1 -1.2 2 2 1 -30.7 75.7 1.3 7 II 26.3 64.6 78.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1498 NM_003342 Huesken UBE2G1 7326 GACACUAAUCAUGAUGGUUuc AACCAUCAUGAUUAGUGUC -0.9 -2.4 0.6 0 -1 2 -34 69.5 1.4 3 II 36.8 42.2 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1499 NM_003342 Huesken UBE2G1 7326 ACACUAAUCAUGAUGGUUUcc AAACCAUCAUGAUUAGUGU -0.9 -2.2 0.6 3 1 2 -32.5 74.1 -4.2 7 II 31.6 58.5 66.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1500 NM_003342 Huesken UBE2G1 7326 ACUAAUCAUGAUGGUUUCCac GGAAACCAUCAUGAUUAGU -3.3 -2.2 0.7 0 3 2 -33.9 74.1 15.4 6 Ia 36.8 58.2 54.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1501 NM_003342 Huesken UBE2G1 7326 AUGAUGGUUUCCACAGUGUgg ACACUGUGGAAACCAUCAU -2.2 -1.1 -0.9 1 1 2 -36.8 64.9 -11.3 7 II 42.1 57.9 89.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1502 NM_003342 Huesken UBE2G1 7326 GAUGGUUUCCACAGUGUGGau CCACACUGUGGAAACCAUC -3.3 -2.4 -3 1 2 2 -39 60.6 -2.6 3 II 52.6 50.5 86.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1503 NM_003342 Huesken UBE2G1 7326 AUGGUUUCCACAGUGUGGAua UCCACACUGUGGAAACCAU -2.4 -1.1 -4.6 3 2 2 -39 65.9 -3.8 5 II 47.4 57.8 85.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1504 NM_003342 Huesken UBE2G1 7326 GGUUUCCACAGUGUGGAUAgg UAUCCACACUGUGGAAACC -1.3 -3.3 -4.9 1 -2 2 -38.2 64.8 1.6 3 III 47.4 30.2 41.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1505 NM_003342 Huesken UBE2G1 7326 UCCACAGUGUGGAUAGGGAgc UCCCUAUCCACACUGUGGA -2.4 -2.4 -4.1 1 1 3 -42 53 -4 4 II 52.6 44.1 62.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1506 NM_003342 Huesken UBE2G1 7326 CCACAGUGUGGAUAGGGAGcc CUCCCUAUCCACACUGUGG -2.1 -3.3 -2 1 0 3 -41.7 40.3 0.7 1 II 57.9 41.5 62.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1507 NM_003342 Huesken UBE2G1 7326 GUGUGGAUAGGGAGCCAGCgu GCUGGCUCCCUAUCCACAC -3.4 -2.2 -0.4 -1 1 3 -44.2 41.4 4.8 2 II 63.2 47.1 64 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1508 NM_003342 Huesken UBE2G1 7326 GGGAGCCAGCGUUCCUCUGgc CAGAGGAACGCUGGCUCCC -2.1 -3.3 -1.6 1 0 3 -45.3 42.5 3 -1 II 68.4 33.2 42.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1509 NM_003342 Huesken UBE2G1 7326 AGCCAGCGUUCCUCUGGCUuu AGCCAGAGGAACGCUGGCU -2.1 -2.1 -7.9 2 1 3 -45.1 39.5 -6 1 II 63.2 38.6 37.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1510 NM_003342 Huesken UBE2G1 7326 GCCAGCGUUCCUCUGGCUUuu AAGCCAGAGGAACGCUGGC -0.9 -3.4 -6.5 0 -1 3 -43.9 45.4 1.4 0 III 63.2 29 35.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1511 NM_003342 Huesken UBE2G1 7326 CAGCGUUCCUCUGGCUUUUca AAAAGCCAGAGGAACGCUG -0.9 -2.1 -0.5 1 -3 3 -39 52.2 -5.3 3 III 52.6 38.9 32.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1512 NM_003342 Huesken UBE2G1 7326 GCGUUCCUCUGGCUUUUCAua UGAAAAGCCAGAGGAACGC -2.1 -3.4 1.1 1 -2 3 -39.3 63 1 3 III 52.6 28.5 35.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1513 NM_003342 Huesken UBE2G1 7326 UCCUCUGGCUUUUCAUAACca GUUAUGAAAAGCCAGAGGA -2.2 -2.4 1 1 1 3 -35.9 79.5 10.4 5 II 42.1 58.3 49.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1514 NM_003342 Huesken UBE2G1 7326 UCUGGCUUUUCAUAACCAUac AUGGUUAUGAAAAGCCAGA -1.1 -2.4 -4.2 1 1 3 -34.6 68.1 -6.3 4 II 36.8 54.6 39.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1515 NM_003342 Huesken UBE2G1 7326 CUGGCUUUUCAUAACCAUAcu UAUGGUUAUGAAAAGCCAG -1.3 -2.1 -4.2 0 -4 3 -33.5 71.7 -3 1 III 36.8 49 31.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1516 NM_003342 Huesken UBE2G1 7326 UUUUCAUAACCAUACUUAUcu AUAAGUAUGGUUAUGAAAA -1.1 -0.9 1.3 1 1 2 -28.1 96.3 -6.3 8 II 21.1 64.5 69.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1517 NM_003342 Huesken UBE2G1 7326 UUUCAUAACCAUACUUAUCuu GAUAAGUAUGGUUAUGAAA -2.4 -0.9 1.3 2 3 2 -29.6 94.8 12.8 7 Ia 26.3 78.4 87.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1518 NM_003342 Huesken UBE2G1 7326 CCAUACUUAUCUUCCCCAGgc CUGGGGAAGAUAAGUAUGG -2.1 -3.3 1 0 0 4 -37.3 68 1.4 4 II 47.4 45 55 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1519 NM_003342 Huesken UBE2G1 7326 UACUUAUCUUCCCCAGGCUca AGCCUGGGGAAGAUAAGUA -2.1 -1.3 0.7 1 2 4 -39.6 71.3 -6.3 7 II 47.4 61 78.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1520 NM_003342 Huesken UBE2G1 7326 UAUCUUCCCCAGGCUCAUGaa CAUGAGCCUGGGGAAGAUA -2.1 -1.3 0.7 2 3 4 -40.8 68.1 2.3 6 Ia 52.6 64.4 76 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1521 NM_003342 Huesken UBE2G1 7326 AUCUUCCCCAGGCUCAUGAag UCAUGAGCCUGGGGAAGAU -2.4 -1.1 0.7 2 1 4 -41.9 72.1 1 7 II 52.6 51.2 76.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1522 NM_003342 Huesken UBE2G1 7326 GGCUCAUGAAGAAUAGAAAug UUUCUAUUCUUCAUGAGCC -0.9 -3.3 0.3 1 -3 3 -33.9 63.3 -4 3 III 36.8 28.3 29.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1523 NM_003342 Huesken UBE2G1 7326 AAUAGAAAUGCACACAUCAcc UGAUGUGUGCAUUUCUAUU -2.1 -0.9 -0.9 1 1 2 -32.5 69 -3.7 7 II 31.6 61.2 74.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1524 NM_003342 Huesken UBE2G1 7326 UAGAAAUGCACACAUCACCau GGUGAUGUGUGCAUUUCUA -3.3 -1.3 -0.9 2 3 2 -36 74.5 10.2 8 Ia 42.1 79.3 94.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1525 NM_003342 Huesken UBE2G1 7326 AGAAAUGCACACAUCACCAuu UGGUGAUGUGUGCAUUUCU -2.1 -2.1 -0.9 1 2 2 -36.8 64.9 -1.4 6 II 42.1 57.6 85 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1526 NM_003342 Huesken UBE2G1 7326 UUUUAUCAACAUUUGGGUGcc CACCCAAAUGUUGAUAAAA -2.1 -0.9 1.8 0 5 3 -30.7 97.2 10.4 7 Ia 31.6 70.3 73.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1527 NM_003342 Huesken UBE2G1 7326 UCAACAUUUGGGUGCCAGAuu UCUGGCACCCAAAUGUUGA -2.4 -2.4 -0.2 0 0 3 -38.9 63.3 -3.8 6 II 47.4 53.2 73.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1528 NM_003342 Huesken UBE2G1 7326 AACAUUUGGGUGCCAGAUUuc AAUCUGGCACCCAAAUGUU -0.9 -0.9 -0.1 3 0 3 -36.4 68.3 -1.6 6 II 42.1 55.9 73.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1529 NM_003342 Huesken UBE2G1 7326 GUGCCAGAUUUCUGUAAUGaa CAUUACAGAAAUCUGGCAC -2.1 -2.2 -2.5 0 0 3 -34.7 55.5 -2.4 1 II 42.1 43 50.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1530 NM_003342 Huesken UBE2G1 7326 AUUUCUGUAAUGAAUUUCAuu UGAAAUUCAUUACAGAAAU -2.1 -1.1 0 1 1 1 -27.8 94.6 -6.3 8 II 21.1 66.1 61.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1531 NM_003342 Huesken UBE2G1 7326 UAAUGAAUUUCAUUUUAGGag CCUAAAAUGAAAUUCAUUA -3.3 -1.3 -1.1 0 5 2 -26.6 96.4 0 6 Ia 21.1 75.7 69.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1532 NM_003342 Huesken UBE2G1 7326 AUGAAUUUCAUUUUAGGAGgu CUCCUAAAAUGAAAUUCAU -2.1 -1.1 0.5 3 4 2 -28.9 98.1 8.1 7 Ia 26.3 71.9 87.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1533 NM_003342 Huesken UBE2G1 7326 GAAUUUCAUUUUAGGAGGUcg ACCUCCUAAAAUGAAAUUC -2.2 -2.4 2.3 -1 1 2 -31.2 69.3 -3.5 4 II 31.6 43.8 39.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1534 NM_003342 Huesken UBE2G1 7326 AUUUUAGGAGGUCGGAGGGga CCCUCCGACCUCCUAAAAU -3.3 -1.1 0 5 3 -39.7 62.4 5.4 7 Ia 52.6 56.3 62.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1535 NM_003342 Huesken UBE2G1 7326 GAGGUCGGAGGGGAUAAUCuu GAUUAUCCCCUCCGACCUC -2.4 -2.4 1.8 0 0 4 -41.7 44.6 7.4 2 II 57.9 44.6 84.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1536 NM_003342 Huesken UBE2G1 7326 AGGUCGGAGGGGAUAAUCUuu AGAUUAUCCCCUCCGACCU -2.1 -2.1 1.8 2 1 4 -41.4 54.8 -4.2 5 II 52.6 50.5 84.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1537 NM_003342 Huesken UBE2G1 7326 CACCUUCAUAAAGUGUAUCug GAUACACUUUAUGAAGGUG -2.4 -2.1 -2.2 0 0 2 -32.7 73.5 10 2 II 36.8 53 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1538 NM_003342 Huesken UBE2G1 7326 ACCUUCAUAAAGUGUAUCUgg AGAUACACUUUAUGAAGGU -2.1 -2.2 0.3 0 0 2 -32.7 86.2 -1.7 7 II 31.6 54.9 78.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1539 NM_003342 Huesken UBE2G1 7326 UAAAGUGUAUCUGGAGGGCca GCCCUCCAGAUACACUUUA -3.4 -1.3 2.5 -1 5 4 -38.5 62.6 8.1 7 Ia 47.4 66.2 75.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1540 NM_003342 Huesken UBE2G1 7326 GUGUAUCUGGAGGGCCAAUaa AUUGGCCCUCCAGAUACAC -1.1 -2.2 -1.5 0 -2 5 -40.7 45.7 1 2 II 52.6 30.8 36.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1541 NM_003342 Huesken UBE2G1 7326 GGAGGGCCAAUAAUAAGGAcu UCCUUAUUAUUGGCCCUCC -2.4 -3.3 -0.2 0 0 5 -38.5 39.3 -4 2 III 47.4 34.9 44.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1542 NM_003342 Huesken UBE2G1 7326 GGCCAAUAAUAAGGACUUCcc GAAGUCCUUAUUAUUGGCC -2.4 -3.3 -0.2 1 -1 4 -35 47.3 12.4 3 II 42.1 34.6 87.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1543 NM_003342 Huesken UBE2G1 7326 GCCAAUAAUAAGGACUUCCca GGAAGUCCUUAUUAUUGGC -3.3 -3.4 -1 0 0 3 -35 66 12.4 4 II 42.1 54.6 71 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1544 NM_003342 Huesken UBE2G1 7326 UAAGGACUUCCCAUCGGUAga UACCGAUGGGAAGUCCUUA -1.3 -1.3 -2 0 2 3 -39 54.8 -8.7 4 II 47.4 54.4 93.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1545 NM_003342 Huesken UBE2G1 7326 GGACUUCCCAUCGGUAGAGau CUCUACCGAUGGGAAGUCC -2.1 -3.3 -0.9 1 1 3 -41.3 41.9 -2.4 2 II 57.9 36.5 68.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1546 NM_003342 Huesken UBE2G1 7326 ACUUCCCAUCGGUAGAGAUca AUCUCUACCGAUGGGAAGU -1.1 -2.2 -2.7 1 1 3 -39.1 63.1 -4 3 II 47.4 38.7 67.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1547 NM_003342 Huesken UBE2G1 7326 CCAUCGGUAGAGAUCAUUGuc CAAUGAUCUCUACCGAUGG -2.1 -3.3 -0.1 -1 0 3 -36.8 63.5 0 4 II 47.4 50.2 86.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1548 NM_003342 Huesken UBE2G1 7326 AUCGGUAGAGAUCAUUGUCau GACAAUGAUCUCUACCGAU -2.4 -1.1 0.6 1 3 3 -36 70.8 15.1 4 Ib 42.1 62.5 103.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1549 NM_003342 Huesken UBE2G1 7326 CGGUAGAGAUCAUUGUCAUcu AUGACAAUGAUCUCUACCG -1.1 -2.4 1.7 -1 -2 3 -35.7 58.5 -3.3 3 III 42.1 34.2 40.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1550 NM_003342 Huesken UBE2G1 7326 UUGUCAUCUAUUAAACCUGca CAGGUUUAAUAGAUGACAA -2.1 -0.9 -0.4 1 3 2 -31.4 86 0.4 7 Ia 31.6 78.3 97.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1551 NM_003342 Huesken UBE2G1 7326 CAUCUAUUAAACCUGCAGAaa UCUGCAGGUUUAAUAGAUG -2.4 -2.1 0.7 1 -1 2 -33.8 78 -1.1 5 II 36.8 48.4 60.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1552 NM_003342 Huesken UBE2G1 7326 UCUAUUAAACCUGCAGAAAag UUUCUGCAGGUUUAAUAGA -0.9 -2.4 1.1 0 -1 2 -32.4 75.4 -3.1 7 II 31.6 51.9 51.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1553 NM_003342 Huesken UBE2G1 7326 UUAAACCUGCAGAAAAGCCuu GGCUUUUCUGCAGGUUUAA -3.3 -0.9 -1.7 1 5 3 -35.2 71.1 9.8 6 Ia 42.1 75.9 83.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1554 NM_003342 Huesken UBE2G1 7326 GAAAAGCCUUCCACUGGAUuu AUCCAGUGGAAGGCUUUUC -1.1 -2.4 -0.6 0 0 3 -37.9 48.5 -8.6 4 II 47.4 34.7 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1555 NM_006357 Huesken UBE2E3 10477 CACUGUCUGGCUAUCCUGUcg ACAGGAUAGCCAGACAGUG -2.2 -2.1 -0.9 0 -1 3 -40.6 61.7 -5.6 3 III 52.6 43.4 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1556 NM_006357 Huesken UBE2E3 10477 CUGUCUGGCUAUCCUGUCGug CGACAGGAUAGCCAGACAG -2.4 -2.1 -0.9 0 0 3 -41.1 68.1 5.7 3 II 57.9 52.8 78 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1557 NM_006357 Huesken UBE2E3 10477 UGUCGUGUUCUGCUCUGUUgg AACAGAGCAGAACACGACA -0.9 -2.1 1 2 2 -38.3 65.3 0.8 5 II 47.4 55.9 76.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1558 NM_006357 Huesken UBE2E3 10477 UCGUGUUCUGCUCUGUUGGuc CCAACAGAGCAGAACACGA -3.3 -2.4 1 3 2 -39.4 77.1 5.4 6 Ib 52.6 66.3 88.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1559 NM_006357 Huesken UBE2E3 10477 GUUGGUCAAAUACUGAGUGgc CACUCAGUAUUUGACCAAC -2.1 -2.2 1 0 3 2 -34.6 64 4.7 3 II 42.1 51.8 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1560 NM_006357 Huesken UBE2E3 10477 UGGUCAAAUACUGAGUGGCua GCCACUCAGUAUUUGACCA -3.4 -2.1 1 0 3 3 -38.2 68.4 8.1 6 Ib 47.4 65.2 90.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1561 NM_006357 Huesken UBE2E3 10477 UCAAAUACUGAGUGGCUAUgc AUAGCCACUCAGUAUUUGA -1.1 -2.4 1.4 -1 0 3 -35.1 73 1 8 II 36.8 57.7 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1562 NM_006357 Huesken UBE2E3 10477 GCUUCCAACCAGAGGAUCCgc GGAUCCUCUGGUUGGAAGC -3.3 -3.4 -2.4 0 1 2 -41.8 55.6 7.1 2 II 57.9 45.2 59.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1563 NM_006357 Huesken UBE2E3 10477 UCCAACCAGAGGAUCCGCAgg UGCGGAUCCUCUGGUUGGA -2.1 -2.4 -1.6 1 1 4 -43.3 51.6 -1.3 4 II 57.9 50.8 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1564 NM_006357 Huesken UBE2E3 10477 CAGAGGAUCCGCAGGGUUGca CAACCCUGCGGAUCCUCUG -2.1 -2.1 -0.2 -1 -1 4 -43 43.1 -6.9 3 II 63.2 46.9 56.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1565 NM_006357 Huesken UBE2E3 10477 GGAUCCGCAGGGUUGCAGUcu ACUGCAACCCUGCGGAUCC -2.2 -3.3 -5.5 0 0 4 -44.1 51.8 -1.6 1 III 63.2 34 71.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1566 NM_006357 Huesken UBE2E3 10477 GGGUUGCAGUCUGUCAAAAgg UUUUGACAGACUGCAACCC -0.9 -3.3 1.1 1 -3 3 -37.6 50.3 -0.8 2 III 47.4 23 50.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1567 NM_006357 Huesken UBE2E3 10477 CUGUCAAAAGGGAACAAAUag AUUUGUUCCCUUUUGACAG -1.1 -2.1 -0.2 -1 -3 3 -32.8 62.8 -8.6 3 II 36.8 43.9 47.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1568 NM_006357 Huesken UBE2E3 10477 UGUCAAAAGGGAACAAAUAga UAUUUGUUCCCUUUUGACA -1.3 -2.1 0.6 2 -1 3 -32 60.7 -3.6 6 II 31.6 53.5 45.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1569 NM_006357 Huesken UBE2E3 10477 AAAAGGGAACAAAUAGACAgc UGUCUAUUUGUUCCCUUUU -2.1 -0.9 3.9 1 2 3 -32 64.4 -1.7 6 II 31.6 58.7 86 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1570 NM_006357 Huesken UBE2E3 10477 AGGGAACAAAUAGACAGCAaa UGCUGUCUAUUUGUUCCCU -2.1 -2.1 2.1 1 0 3 -36.9 43.1 -1.1 4 II 42.1 46.8 73.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1571 NM_006357 Huesken UBE2E3 10477 ACAAAUAGACAGCAAAACCuu GGUUUUGCUGUCUAUUUGU -3.3 -2.2 1.1 1 3 2 -33.1 69.6 14.8 6 Ia 36.8 67.2 94.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1572 NM_006357 Huesken UBE2E3 10477 AUAGACAGCAAAACCUUUGaa CAAAGGUUUUGCUGUCUAU -2.1 -1.1 0.8 2 3 2 -33 73.2 2.4 8 Ia 36.8 71.8 92.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1573 NM_006357 Huesken UBE2E3 10477 GCAAAACCUUUGAAAUAGUca ACUAUUUCAAAGGUUUUGC -2.2 -3.4 1.2 0 -1 2 -30.6 53.4 -3.9 3 II 31.6 36.7 34.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1574 NM_006357 Huesken UBE2E3 10477 AAAUAGUCAAAGCGGGACUcc AGUCCCGCUUUGACUAUUU -2.1 -0.9 -1.8 1 2 5 -36 69.2 3.4 7 II 42.1 60.3 56.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1575 NM_006357 Huesken UBE2E3 10477 AUAGUCAAAGCGGGACUCCag GGAGUCCCGCUUUGACUAU -3.3 -1.1 -2.2 0 4 5 -39.9 51.9 5.1 6 Ia 52.6 64.4 69.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1576 NM_006357 Huesken UBE2E3 10477 AGUCAAAGCGGGACUCCAGuu CUGGAGUCCCGCUUUGACU -2.1 -2.1 -1.5 3 3 5 -41.7 45.4 0.1 3 Ia 57.9 49 72 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1577 NM_006357 Huesken UBE2E3 10477 GGGACUCCAGUUGUCUUUAag UAAAGACAACUGGAGUCCC -1.3 -3.3 -1.2 0 -3 3 -38.2 59.6 1.6 1 III 47.4 30.8 43.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1578 NM_006357 Huesken UBE2E3 10477 ACUCCAGUUGUCUUUAAGGau CCUUAAAGACAACUGGAGU -3.3 -2.2 0.3 2 4 2 -35.5 70.9 0 4 II 42.1 58.8 58.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1579 NM_006357 Huesken UBE2E3 10477 GGAUGUCCAGACAGAUGACuc GUCAUCUGUCUGGACAUCC -2.2 -3.3 -1.3 -1 1 2 -40 46.1 4.8 1 II 52.6 33.9 43.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1580 NM_006357 Huesken UBE2E3 10477 UGUCCAGACAGAUGACUCCcu GGAGUCAUCUGUCUGGACA -3.3 -2.1 -1.5 1 3 2 -41 61.8 7.4 6 II 52.6 64.1 75.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1581 NM_006357 Huesken UBE2E3 10477 CAGACAGAUGACUCCCUGAcu UCAGGGAGUCAUCUGUCUG -2.4 -2.1 -1.9 -1 -3 3 -40.9 55.2 -5.8 3 III 52.6 41.8 49 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1582 NM_006357 Huesken UBE2E3 10477 AGACAGAUGACUCCCUGACug GUCAGGGAGUCAUCUGUCU -2.2 -2.1 -1.9 3 3 3 -41 57.6 13.2 5 Ib 52.6 55.9 83.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1583 NM_006357 Huesken UBE2E3 10477 AGAUGACUCCCUGACUGUUga AACAGUCAGGGAGUCAUCU -0.9 -2.1 0.1 2 1 3 -39.5 53.6 -3.3 4 II 47.4 42.6 58.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1584 NM_006357 Huesken UBE2E3 10477 AUGACUCCCUGACUGUUGAug UCAACAGUCAGGGAGUCAU -2.4 -1.1 2.3 2 1 3 -39.5 71.1 1 5 II 47.4 49.1 74.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1585 NM_006357 Huesken UBE2E3 10477 UGACUCCCUGACUGUUGAUgu AUCAACAGUCAGGGAGUCA -1.1 -2.1 2 0 1 3 -39.5 62 -4 5 II 47.4 45.7 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1586 NM_006357 Huesken UBE2E3 10477 ACUCCCUGACUGUUGAUGUug ACAUCAACAGUCAGGGAGU -2.2 -2.2 2 3 2 3 -39.3 70.1 -1.6 5 II 47.4 50.6 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1587 NM_006357 Huesken UBE2E3 10477 CCCUGACUGUUGAUGUUGCag GCAACAUCAACAGUCAGGG -3.4 -3.3 2 0 0 3 -39 53.4 5.1 2 II 52.6 39.2 66.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1588 NM_006357 Huesken UBE2E3 10477 CUGUUGAUGUUGCAGUGAUag AUCACUGCAACAUCAACAG -1.1 -2.1 0.6 0 -2 2 -35.6 61.4 -3.6 4 II 42.1 41.8 69.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1589 NM_006357 Huesken UBE2E3 10477 AGUGAUAGAUUCUGGUGCGga CGCACCAGAAUCUAUCACU -2.4 -2.1 1 0 4 3 -37.7 59.3 0.4 5 Ia 47.4 56.6 73.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1590 NM_006357 Huesken UBE2E3 10477 GAUAGAUUCUGGUGCGGAAag UUCCGCACCAGAAUCUAUC -0.9 -2.4 1.5 1 -1 4 -37.9 56.5 -3.8 4 II 47.4 29.4 42.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1591 NM_006357 Huesken UBE2E3 10477 GAUUCUGGUGCGGAAAGUAac UACUUUCCGCACCAGAAUC -1.3 -2.4 1.3 0 -1 4 -37.5 50.8 -6.1 4 II 47.4 35.8 49.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1592 NM_006357 Huesken UBE2E3 10477 UCUGGUGCGGAAAGUAACCuu GGUUACUUUCCGCACCAGA -3.3 -2.4 -0.8 0 3 4 -39.5 53.5 7.1 5 II 52.6 66.2 91.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1593 NM_006357 Huesken UBE2E3 10477 GGUGCGGAAAGUAACCUUUgg AAAGGUUACUUUCCGCACC -0.9 -3.3 -0.8 0 -2 4 -36.8 55 -3.5 4 III 47.4 39.3 50.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1594 NM_006357 Huesken UBE2E3 10477 CGGAAAGUAACCUUUGGUGgc CACCAAAGGUUACUUUCCG -2.1 -2.4 -0.8 -1 0 3 -35.5 62 -1.7 4 II 47.4 45.9 58.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1595 NM_006357 Huesken UBE2E3 10477 AACCUUUGGUGGCUUAAAUgg AUUUAAGCCACCAAAGGUU -1.1 -0.9 -2.3 4 1 3 -33.9 77.7 0.8 4 II 36.8 50 64.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1596 NM_006357 Huesken UBE2E3 10477 UGGUGGCUUAAAUGGAUAAuc UUAUCCAUUUAAGCCACCA -0.9 -2.1 1.8 -1 -2 3 -34.7 69.3 -1.5 6 II 36.8 47.1 28.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1597 NM_006357 Huesken UBE2E3 10477 GCUUAAAUGGAUAAUCUGAug UCAGAUUAUCCAUUUAAGC -2.4 -3.4 1.5 1 -2 2 -31.8 68.7 1.7 5 II 31.6 38.5 38.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1598 NM_006357 Huesken UBE2E3 10477 CUGAUGAAAAUGUGAUAUCca GAUAUCACAUUUUCAUCAG -2.4 -2.1 1.1 -2 -1 1 -30.7 72.7 5.4 5 II 31.6 58.1 57.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1599 NM_006357 Huesken UBE2E3 10477 UGAAAAUGUGAUAUCCAGAaa UCUGGAUAUCACAUUUUCA -2.4 -2.1 0.8 1 1 2 -32.9 77.9 4 7 II 31.6 63.3 68.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1600 NM_006357 Huesken UBE2E3 10477 AAAACACACCACCUUCAUAua UAUGAAGGUGGUGUGUUUU -1.3 -0.9 2.6 2 1 2 -34.3 71.5 0.9 5 II 36.8 49.3 50.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1601 NM_006357 Huesken UBE2E3 10477 ACACCACCUUCAUAUACAGaa CUGUAUAUGAAGGUGGUGU -2.1 -2.2 0.8 2 3 2 -36.1 57.3 -2.4 3 II 42.1 47.7 36.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1602 NM_006357 Huesken UBE2E3 10477 CAGAACCCGGUGGACCAAGua CUUGGUCCACCGGGUUCUG -2.1 -2.1 -4.2 0 -1 5 -42.6 35.7 0.7 1 II 63.2 41.9 68.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1603 NM_006357 Huesken UBE2E3 10477 UGGACCAAGUAUAGUUGAUcu AUCAACUAUACUUGGUCCA -1.1 -2.1 -0.7 0 0 2 -35.1 70.4 -1.2 5 II 36.8 47.7 59.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1604 NM_006357 Huesken UBE2E3 10477 GACCAAGUAUAGUUGAUCUcc AGAUCAACUAUACUUGGUC -2.1 -2.4 -3.3 1 0 2 -34.2 71.9 3.4 3 III 36.8 43.1 52.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1605 NM_006357 Huesken UBE2E3 10477 UAUAGUUGAUCUCCAUUCAua UGAAUGGAGAUCAACUAUA -2.1 -1.3 0.1 1 1 2 -33.3 89.1 -0.7 8 II 31.6 65 90.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1606 NM_006357 Huesken UBE2E3 10477 AUUCAUAAAUGUUAUCUCCuu GGAGAUAACAUUUAUGAAU -3.3 -1.1 1.6 2 4 2 -29.6 93.9 13.1 7 Ia 26.3 73.7 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1607 NM_006357 Huesken UBE2E3 10477 UCAUAAAUGUUAUCUCCUUua AAGGAGAUAACAUUUAUGA -0.9 -2.4 1.6 1 1 2 -30.6 76.8 -1.3 7 II 26.3 60.8 52 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1608 NM_006357 Huesken UBE2E3 10477 UAUCUCCUUUAGGCCCAGCac GCUGGGCCUAAAGGAGAUA -3.4 -1.3 -0.7 1 4 5 -40.8 68.3 9.7 6 Ib 52.6 65.9 67.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1609 NM_006357 Huesken UBE2E3 10477 UCCUUUAGGCCCAGCACUGca CAGUGCUGGGCCUAAAGGA -2.1 -2.4 -0.7 0 2 5 -42.4 52.9 -7.3 5 Ia 57.9 59.5 73.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1610 NM_006357 Huesken UBE2E3 10477 AGGCCCAGCACUGCAAUUAgg UAAUUGCAGUGCUGGGCCU -1.3 -2.1 0 3 -2 5 -41.2 53 -3.1 5 II 52.6 43.1 47.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1611 NM_006357 Huesken UBE2E3 10477 CCAGCACUGCAAUUAGGAGga CUCCUAAUUGCAGUGCUGG -2.1 -3.3 0.8 0 1 2 -39 48.7 2.6 1 II 52.6 35 51.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1612 NM_006357 Huesken UBE2E3 10477 GCACUGCAAUUAGGAGGAGga CUCCUCCUAAUUGCAGUGC -2.1 -3.4 2.1 0 1 2 -39.3 27.6 0 2 II 52.6 27 34.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1613 NM_006357 Huesken UBE2E3 10477 CACUGCAAUUAGGAGGAGGau CCUCCUCCUAAUUGCAGUG -3.3 -2.1 2.1 -1 0 2 -39.2 52.7 0.3 3 II 52.6 46.8 62.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1614 NM_006357 Huesken UBE2E3 10477 AUUAGGAGGAGGAUCAAGGgu CCUUGAUCCUCCUCCUAAU -3.3 -1.1 1.9 2 5 2 -38.6 66.8 -0.3 7 Ia 47.4 70.3 81.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1615 NM_006357 Huesken UBE2E3 10477 AUCAAGGGUUAUUUCAGCUag AGCUGAAAUAACCCUUGAU -2.1 -1.1 3.4 1 3 3 -34.6 77.9 6.4 6 II 36.8 61 82 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1616 NM_006357 Huesken UBE2E3 10477 GGUUAUUUCAGCUAGCUCCuu GGAGCUAGCUGAAAUAACC -3.3 -3.3 0.5 2 1 2 -37.3 80.7 7.8 6 II 47.4 58.8 80.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1617 NM_006357 Huesken UBE2E3 10477 UAUUUCAGCUAGCUCCUUCug GAAGGAGCUAGCUGAAAUA -2.4 -1.3 0.5 1 4 2 -36.3 90.6 14.4 9 Ia 42.1 73.9 88.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1618 NM_006357 Huesken UBE2E3 10477 UUCAGCUAGCUCCUUCUGAau UCAGAAGGAGCUAGCUGAA -2.4 -0.9 -1.7 2 1 2 -39.6 70.4 -1.4 6 II 47.4 60.3 87.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1619 NM_006357 Huesken UBE2E3 10477 CAGCUAGCUCCUUCUGAAUuc AUUCAGAAGGAGCUAGCUG -1.1 -2.1 0.5 0 -3 2 -38.3 58.9 -5.3 3 III 47.4 36.7 42.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1620 NM_006357 Huesken UBE2E3 10477 AGCUAGCUCCUUCUGAAUUcu AAUUCAGAAGGAGCUAGCU -0.9 -2.1 0.7 2 0 2 -37.1 69.4 6.5 4 II 42.1 46.1 71.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1621 NM_006357 Huesken UBE2E3 10477 UUCUGAAUUCUUUUAGCACua GUGCUAAAAGAAUUCAGAA -2.2 -0.9 2.6 0 4 2 -31.1 89.6 12.8 6 Ia 31.6 70.2 81.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1622 NM_006357 Huesken UBE2E3 10477 ACUAGUGGAUAACUUAGCAgu UGCUAAGUUAUCCACUAGU -2.1 -2.2 0.4 1 2 2 -35.1 68.2 3.3 5 II 36.8 49.3 82.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1623 NM_006357 Huesken UBE2E3 10477 GCAGUGGUUUUGCUAGAGAgu UCUCUAGCAAAACCACUGC -2.4 -3.4 -0.3 0 -1 2 -38 46.5 1 3 III 47.4 33.6 35.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1624 NM_006357 Huesken UBE2E3 10477 GUGGUUUUGCUAGAGAGUUug AACUCUCUAGCAAAACCAC -0.9 -2.2 2.6 2 -1 2 -35.6 57.1 -4 3 II 42.1 47 52.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1625 NM_006357 Huesken UBE2E3 10477 GUUUUGCUAGAGAGUUUGGug CCAAACUCUCUAGCAAAAC -3.3 -2.2 2.6 -1 2 2 -34.3 69.7 -0.3 5 II 42.1 46.9 69.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1626 NM_006357 Huesken UBE2E3 10477 UUUGCUAGAGAGUUUGGUGuu CACCAAACUCUCUAGCAAA -2.1 -0.9 2.6 0 5 2 -35.5 84.4 4.6 6 Ia 42.1 72.1 84.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1627 NM_006357 Huesken UBE2E3 10477 UUGCUAGAGAGUUUGGUGUuu ACACCAAACUCUCUAGCAA -2.2 -0.9 2.6 2 2 2 -36.8 79.9 1.4 8 II 42.1 65.2 90.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1628 NM_006357 Huesken UBE2E3 10477 CUGGGUGGCAGAAGGUUUUcu AAAACCUUCUGCCACCCAG -0.9 -2.1 0.6 -1 -3 3 -39.6 45.8 -8.6 4 III 52.6 42.6 32.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1629 NM_006357 Huesken UBE2E3 10477 UCUUUCCUCUUGUUCUUCAgg UGAAGAACAAGAGGAAAGA -2.1 -2.4 2.1 1 1 2 -34.6 88.4 -1.4 7 II 36.8 57.4 89.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1630 NM_006357 Huesken UBE2E3 10477 UCCUCUUGUUCUUCAGGCUcu AGCCUGAAGAACAAGAGGA -2.1 -2.4 -0.9 1 1 3 -39.2 75.8 -3.3 5 II 47.4 56.4 89 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1631 NM_006357 Huesken UBE2E3 10477 UGGAGCGGCUGGGUCUCGCug GCGAGACCCAGCCGCUCCA -3.4 -2.1 -2.1 1 4 5 -48.1 43.6 9.7 3 II 73.7 57.1 69.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1632 NM_006357 Huesken UBE2E3 10477 CGGCUGGGUCUCGCUGGUCcg GACCAGCGAGACCCAGCCG -2.4 -2.4 -1 0 -1 4 -46.9 25 3.1 0 II 73.7 37.8 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1633 NM_006357 Huesken UBE2E3 10477 CGCAUCUGAACUGCCACUGcu CAGUGGCAGUUCAGAUGCG -2.1 -2.4 -2.4 0 -1 3 -40.5 57.5 -1.3 2 II 57.9 47.2 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1634 NM_021988 Huesken UBE2V1 7335 GUCCUUCGGGCGGCUGAGGga CCUCAGCCGCCCGAAGGAC -3.3 -2.2 -0.9 2 1 8 -46.8 32.7 -2.4 1 II 73.7 37.3 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1635 NM_021988 Huesken UBE2V1 7335 CCUUCGGGCGGCUGAGGGAgu UCCCUCAGCCGCCCGAAGG -2.4 -3.3 0.2 -1 -2 8 -47.9 27.8 -8.1 2 III 73.7 24 46.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1636 NM_021988 Huesken UBE2V1 7335 UUUCAUAUUUUCUUUAGACau GUCUAAAGAAAAUAUGAAA -2.2 -0.9 1 1 5 1 -26.8 101.1 10.1 7 Ia 21.1 77.5 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1637 NM_021988 Huesken UBE2V1 7335 UUCUUUAGACAUCAUUAGGcg CCUAAUGAUGUCUAAAGAA -3.3 -0.9 1 0 3 2 -31.6 95.8 7.7 7 Ia 31.6 74.1 95.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1638 NM_021988 Huesken UBE2V1 7335 UCUUUAGACAUCAUUAGGCgc GCCUAAUGAUGUCUAAAGA -3.4 -2.4 1.8 1 5 3 -34.1 81.4 4.8 8 Ia 36.8 73.4 94.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1639 NM_021988 Huesken UBE2V1 7335 AGACAUCAUUAGGCGCCGAag UCGGCGCCUAAUGAUGUCU -2.4 -2.1 -1.4 2 1 7 -40.4 43.2 1.3 3 II 52.6 40.6 78.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1640 NM_021988 Huesken UBE2V1 7335 UUAGGCGCCGAAGCUCUUGca CAAGAGCUUCGGCGCCUAA -2.1 -0.9 -4.5 1 3 7 -40.9 54.3 2.3 5 II 57.9 68.1 84.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1641 NM_021988 Huesken UBE2V1 7335 UAGGCGCCGAAGCUCUUGCag GCAAGAGCUUCGGCGCCUA -3.4 -1.3 -4.5 1 4 7 -43.4 63.4 14.4 4 II 63.2 67.3 82.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1642 NM_021988 Huesken UBE2V1 7335 CGAAGCUCUUGCAGGACAAcu UUGUCCUGCAAGAGCUUCG -0.9 -2.4 -0.5 -1 -3 2 -39.3 43.7 -10.7 3 III 52.6 30.2 51.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1643 NM_021988 Huesken UBE2V1 7335 CUCUUGCAGGACAACUUUGau CAAAGUUGUCCUGCAAGAG -2.1 -2.1 -0.1 0 -1 2 -36.3 60.8 -4.6 4 II 47.4 50.3 71.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1644 NM_021988 Huesken UBE2V1 7335 UCUUGCAGGACAACUUUGAug UCAAAGUUGUCCUGCAAGA -2.4 -2.4 -0.1 1 0 2 -36.6 66.9 -8.7 8 II 42.1 55.6 89.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1645 NM_021988 Huesken UBE2V1 7335 GGACAACUUUGAUGCUAUAug UAUAGCAUCAAAGUUGUCC -1.3 -3.3 -1.4 0 -3 2 -33.9 50.3 -1.1 1 III 36.8 24 47 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1646 NM_021988 Huesken UBE2V1 7335 ACAACUUUGAUGCUAUAUGaa CAUAUAGCAUCAAAGUUGU -2.1 -2.2 -1.3 3 3 2 -31.4 85.8 4.7 5 Ia 31.6 66.1 77.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1647 NM_021988 Huesken UBE2V1 7335 CAACUUUGAUGCUAUAUGAau UCAUAUAGCAUCAAAGUUG -2.4 -2.1 0 1 -2 2 -31.6 78.4 -8.1 5 II 31.6 49.3 49 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1648 NM_021988 Huesken UBE2V1 7335 CUUUGAUGCUAUAUGAAUUcu AAUUCAUAUAGCAUCAAAG -0.9 -2.1 3.2 1 -1 2 -29.3 85.6 -0.9 4 II 26.3 50.8 70 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1649 NM_021988 Huesken UBE2V1 7335 UGAUGCUAUAUGAAUUCUGcc CAGAAUUCAUAUAGCAUCA -2.1 -2.1 2.1 1 3 2 -32 80.2 -2.6 7 Ib 31.6 73.2 90 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1650 NM_021988 Huesken UBE2V1 7335 GAUGCUAUAUGAAUUCUGCca GCAGAAUUCAUAUAGCAUC -3.4 -2.4 0.1 0 3 2 -33.3 80.1 7.1 4 II 36.8 56.6 82 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1651 NM_021988 Huesken UBE2V1 7335 UGCUAUAUGAAUUCUGCCAuu UGGCAGAAUUCAUAUAGCA -2.1 -2.1 0.1 1 0 3 -35.2 87.5 4.3 7 II 36.8 62.4 89.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1652 NM_021988 Huesken UBE2V1 7335 GAAUUCUGCCAUUUUGCUAgc UAGCAAAAUGGCAGAAUUC -1.3 -2.4 -1.3 2 0 3 -33.4 83.9 3.9 4 II 36.8 44.5 63 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1653 NM_021988 Huesken UBE2V1 7335 UUCUGCCAUUUUGCUAGCAcu UGCUAGCAAAAUGGCAGAA -2.1 -0.9 -4.6 0 1 3 -36.6 67.7 -0.7 4 II 42.1 54.8 71.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1654 NM_021988 Huesken UBE2V1 7335 UGCCAUUUUGCUAGCACUGau CAGUGCUAGCAAAAUGGCA -2.1 -2.1 -4 1 2 3 -37.6 65.4 0.8 4 Ib 47.4 64.1 87.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1655 NM_021988 Huesken UBE2V1 7335 UUGCUAGCACUGAUAUGGCuc GCCAUAUCAGUGCUAGCAA -3.4 -0.9 0.4 1 5 3 -38.5 64 7.1 6 Ib 47.4 69.1 92.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1656 NM_021988 Huesken UBE2V1 7335 GCUAGCACUGAUAUGGCUCuu GAGCCAUAUCAGUGCUAGC -2.4 -3.4 -0.5 0 2 3 -40 61.1 12.5 3 II 52.6 47.9 90.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1657 NM_021988 Huesken UBE2V1 7335 CUAGCACUGAUAUGGCUCUug AGAGCCAUAUCAGUGCUAG -2.1 -2.1 -0.5 -1 -1 3 -38.7 54.5 -6 4 III 47.4 46.8 90.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1658 NM_021988 Huesken UBE2V1 7335 UAGCACUGAUAUGGCUCUUgg AAGAGCCAUAUCAGUGCUA -0.9 -1.3 -0.5 1 1 3 -37.5 65.2 4.1 6 II 42.1 55.2 84.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1659 NM_021988 Huesken UBE2V1 7335 UAUGGCUCUUGGGUCCACCac GGUGGACCCAAGAGCCAUA -3.3 -1.3 -2.3 1 5 3 -42.9 65.9 9.7 4 Ib 57.9 72.2 84.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1660 NM_021988 Huesken UBE2V1 7335 UUGGGUCCACCACUCCAUUag AAUGGAGUGGUGGACCCAA -0.9 -0.9 -1.3 0 1 3 -41.3 57.4 -1.6 3 II 52.6 57.6 83.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1661 NM_021988 Huesken UBE2V1 7335 CCACCACUCCAUUAGAACUau AGUUCUAAUGGAGUGGUGG -2.1 -3.3 0.3 1 -2 2 -38.1 60.1 -0.7 1 III 47.4 40.4 56.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1662 NM_021988 Huesken UBE2V1 7335 GUUACAAAUCUUACAAAGGgg CCUUUGUAAGAUUUGUAAC -3.3 -2.2 1.8 0 2 2 -29.8 74.8 0.4 4 II 31.6 57.3 63.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1663 NM_021988 Huesken UBE2V1 7335 GGUCCACAUUCUAUUUUAAgg UUAAAAUAGAAUGUGGACC -0.9 -3.3 3.2 1 -2 2 -31.4 67.9 -3.3 2 III 31.6 23.7 38.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1664 NM_021988 Huesken UBE2V1 7335 UAUUUUAAGGCUGUAUAUUcg AAUAUACAGCCUUAAAAUA -0.9 -1.3 2.6 1 2 3 -28.2 96.4 -1 8 II 21.1 68.7 82.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1665 NM_021988 Huesken UBE2V1 7335 UUUUAAGGCUGUAUAUUCGgu CGAAUAUACAGCCUUAAAA -2.4 -0.9 2.6 1 5 3 -30.6 90.9 5.5 9 Ia 31.6 74.7 89.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1666 NM_021988 Huesken UBE2V1 7335 UAAGGCUGUAUAUUCGGUUuu AACCGAAUAUACAGCCUUA -0.9 -1.3 3.4 1 3 3 -34.3 76.4 -1.6 7 II 36.8 70.6 96.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1667 NM_021988 Huesken UBE2V1 7335 CAUAAAUUGUUCUUGGAGGcc CCUCCAAGAACAAUUUAUG -3.3 -2.1 2.5 1 2 2 -32.1 79 0.7 5 II 36.8 57.7 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1668 NM_021988 Huesken UBE2V1 7335 AUAAAUUGUUCUUGGAGGCcc GCCUCCAAGAACAAUUUAU -3.4 -1.1 2.5 1 5 3 -33.4 79.7 10.8 7 Ia 36.8 68.8 76.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1669 NM_021988 Huesken UBE2V1 7335 AAUUGUUCUUGGAGGCCCAau UGGGCCUCCAAGAACAAUU -2.1 -0.9 -1.3 1 2 5 -38.8 62.7 -6.3 5 II 47.4 53 57.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1670 NM_021988 Huesken UBE2V1 7335 GGAGGCCCAAUUAUCAUCCcu GGAUGAUAAUUGGGCCUCC -3.3 -3.3 0.8 0 2 5 -39.8 58.6 10.2 3 II 52.6 52.7 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1671 NM_021988 Huesken UBE2V1 7335 UUAUCAUCCCUGUCCAUCUug AGAUGGACAGGGAUGAUAA -2.1 -0.9 0.8 2 2 3 -37.7 84.5 -4 8 II 42.1 73.6 90 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1672 NM_021988 Huesken UBE2V1 7335 CAUCCCUGUCCAUCUUGUAag UACAAGAUGGACAGGGAUG -1.3 -2.1 1.9 1 -2 3 -38.5 61.6 -8.1 3 III 47.4 37.3 52.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1673 NM_021988 Huesken UBE2V1 7335 UCAUGUCUUCGUCAUCUUCua GAAGAUGACGAAGACAUGA -2.4 -2.4 1 0 2 2 -35.7 79 12.8 6 Ib 42.1 64.3 95 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1674 NM_021988 Huesken UBE2V1 7335 UGUCUUCGUCAUCUUCUAGac CUAGAAGAUGACGAAGACA -2.1 -2.1 2.8 1 3 2 -35.6 83.5 10.1 6 Ib 42.1 59 88.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1675 NM_021988 Huesken UBE2V1 7335 GUCUUCGUCAUCUUCUAGAcc UCUAGAAGAUGACGAAGAC -2.4 -2.2 1.2 1 -1 2 -35.9 77.1 -3.8 5 III 42.1 46 58 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1676 NM_021988 Huesken UBE2V1 7335 UCUUCGUCAUCUUCUAGACcc GUCUAGAAGAUGACGAAGA -2.2 -2.4 -2.7 1 3 2 -35.9 85.2 8.1 5 Ib 42.1 61.1 92 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1677 NM_021988 Huesken UBE2V1 7335 UUCGUCAUCUUCUAGACCCca GGGUCUAGAAGAUGACGAA -3.3 -0.9 -2.7 1 4 3 -38 77.6 5.1 5 Ib 47.4 79.5 96.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1678 NM_021988 Huesken UBE2V1 7335 CGUCAUCUUCUAGACCCCAgc UGGGGUCUAGAAGAUGACG -2.1 -2.4 -2.7 0 -2 4 -40.1 40.3 -3.1 1 III 52.6 37.9 38.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1679 NM_021988 Huesken UBE2V1 7335 CAUCUUCUAGACCCCAGCUaa AGCUGGGGUCUAGAAGAUG -2.1 -2.1 -0.8 0 0 4 -40.7 62.6 -3.6 3 II 52.6 47.7 73 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1680 NM_021988 Huesken UBE2V1 7335 AUCUUCUAGACCCCAGCUAac UAGCUGGGGUCUAGAAGAU -1.3 -1.1 -0.8 3 0 4 -39.9 66 -6.1 7 II 47.4 51.4 82.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1681 NM_021988 Huesken UBE2V1 7335 GCUAACUGUGCCAUCUCCUac AGGAGAUGGCACAGUUAGC -2.1 -3.4 1 1 1 3 -40.6 55.9 -6.2 4 II 52.6 44.3 60.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1682 NM_021988 Huesken UBE2V1 7335 UAACUGUGCCAUCUCCUACuc GUAGGAGAUGGCACAGUUA -2.2 -1.3 0.8 3 4 3 -38.6 81.3 17.5 8 Ia 47.4 72.9 88.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1683 NM_021988 Huesken UBE2V1 7335 UGUGCCAUCUCCUACUCCUuu AGGAGUAGGAGAUGGCACA -2.1 -2.1 0.6 1 2 3 -42 68 -8.7 5 II 52.6 61.4 92.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1684 NM_021988 Huesken UBE2V1 7335 CCAUCUCCUACUCCUUUCUgg AGAAAGGAGUAGGAGAUGG -2.1 -3.3 3 -1 -2 2 -38.5 71.5 -2.9 4 III 47.4 43.6 58.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1685 NM_021988 Huesken UBE2V1 7335 UACUCCUUUCUGGCCUUCUuc AGAAGGCCAGAAAGGAGUA -2.1 -1.3 -0.5 1 1 4 -39.3 78.4 -4 7 II 47.4 64.9 86.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1686 NM_021988 Huesken UBE2V1 7335 GGCCUUCUUCGAGUUCUUCca GAAGAACUCGAAGAAGGCC -2.4 -3.3 1 1 0 4 -38.6 57.8 9.7 2 II 52.6 38.3 53.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1687 NM_021988 Huesken UBE2V1 7335 CCUUCUUCGAGUUCUUCCAac UGGAAGAACUCGAAGAAGG -2.1 -3.3 1 1 -2 2 -37.3 77.5 -2.7 4 II 47.4 43.7 59.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1688 NM_021988 Huesken UBE2V1 7335 GUUCUUCCAACAGUCGGAAau UUCCGACUGUUGGAAGAAC -0.9 -2.2 -3.4 1 0 3 -37.2 55.8 -3.8 3 II 47.4 34.3 52.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1689 NM_021988 Huesken UBE2V1 7335 UUCCAACAGUCGGAAAUUGcg CAAUUUCCGACUGUUGGAA -2.1 -0.9 -2.8 2 2 3 -34.6 56.1 0.4 5 Ib 42.1 58.5 95.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1690 NM_021988 Huesken UBE2V1 7335 CAACAGUCGGAAAUUGCGAgg UCGCAAUUUCCGACUGUUG -2.4 -2.1 0.2 2 0 3 -36.2 51.5 -1 4 II 47.4 46.5 85.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1691 NM_021988 Huesken UBE2V1 7335 CAGUCGGAAAUUGCGAGGGac CCCUCGCAAUUUCCGACUG -3.3 -2.1 0.3 -1 1 3 -39.7 52.5 1 3 II 57.9 51.3 84.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1692 NM_021988 Huesken UBE2V1 7335 UCGGAAAUUGCGAGGGACUuu AGUCCCUCGCAAUUUCCGA -2.1 -2.4 0.8 -1 0 3 -40 44.5 -6.2 5 II 52.6 54.2 96 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1693 NM_021988 Huesken UBE2V1 7335 AUUGCGAGGGACUUUUACUcc AGUAAAAGUCCCUCGCAAU -2.1 -1.1 1.1 2 3 3 -36 74.9 -1.7 5 II 42.1 61.7 91 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1694 NM_021988 Huesken UBE2V1 7335 UGCGAGGGACUUUUACUCCuu GGAGUAAAAGUCCCUCGCA -3.3 -2.1 -0.8 0 3 3 -39.7 63.4 15.5 6 II 52.6 65.9 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1695 NM_021988 Huesken UBE2V1 7335 GAGGGACUUUUACUCCUUUgc AAAGGAGUAAAAGUCCCUC -0.9 -2.4 -1 0 -1 3 -35.7 54.5 0.8 1 III 42.1 37.6 65.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1696 NM_021988 Huesken UBE2V1 7335 UUUACUCCUUUGCAGUGAAau UUCACUGCAAAGGAGUAAA -0.9 -0.9 0 0 1 2 -34.3 76.3 -1.4 6 II 36.8 53.9 81.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1697 NM_021988 Huesken UBE2V1 7335 UACUCCUUUGCAGUGAAAUuu AUUUCACUGCAAAGGAGUA -1.1 -1.3 -0.9 1 1 2 -34.5 82.9 -4 6 II 36.8 59.9 95 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1698 NM_021988 Huesken UBE2V1 7335 CUCCUUUGCAGUGAAAUUUuc AAAUUUCACUGCAAAGGAG -0.9 -2.1 0.3 2 -3 2 -32.8 74.7 -3 5 II 36.8 51.1 45.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1699 NM_021988 Huesken UBE2V1 7335 CCUUUGCAGUGAAAUUUUCua GAAAAUUUCACUGCAAAGG -2.4 -3.3 0.3 0 -1 2 -31.6 65.8 2.8 4 II 36.8 44.4 83.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1700 NM_021988 Huesken UBE2V1 7335 UUGCAGUGAAAUUUUCUAGgu CUAGAAAAUUUCACUGCAA -2.1 -0.9 1 2 3 2 -30.8 94.3 10.4 8 Ib 31.6 73.5 96 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1701 NM_021988 Huesken UBE2V1 7335 GCAGUGAAAUUUUCUAGGUuc ACCUAGAAAAUUUCACUGC -2.2 -3.4 1 0 0 2 -33.3 62.6 -1 3 III 36.8 41.8 36.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1702 NM_021988 Huesken UBE2V1 7335 CAGUGAAAUUUUCUAGGUUca AACCUAGAAAAUUUCACUG -0.9 -2.1 1 -1 -1 2 -30.8 68.4 1.8 3 II 31.6 43.5 49.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1703 NM_021988 Huesken UBE2V1 7335 GUGAAAUUUUCUAGGUUCAag UGAACCUAGAAAAUUUCAC -2.1 -2.2 0.9 0 -2 2 -31.1 70.7 -3 5 II 31.6 42.7 43 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1704 NM_021988 Huesken UBE2V1 7335 GAAAUUUUCUAGGUUCAAGuc CUUGAACCUAGAAAAUUUC -2.1 -2.4 1.9 2 2 2 -29.8 85.9 4.6 5 II 31.6 54.6 53.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1705 NM_021988 Huesken UBE2V1 7335 AUUUUCUAGGUUCAAGUCUuc AGACUUGAACCUAGAAAAU -2.1 -1.1 1.4 3 2 2 -32.3 86.6 1.5 8 II 31.6 66 71.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1706 NM_021988 Huesken UBE2V1 7335 UCUAGGUUCAAGUCUUCCUuc AGGAAGACUUGAACCUAGA -2.1 -2.4 -0.2 2 2 2 -37.2 82.8 -1.7 7 II 42.1 67.6 78 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1707 NM_021988 Huesken UBE2V1 7335 AGUCUUCCUUCAUCACUCAgu UGAGUGAUGAAGGAAGACU -2.1 -2.1 1.3 2 0 2 -37.3 65.5 -6.1 5 II 42.1 46.8 62.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1708 NM_022005 Huesken Fxyd6 53826 GCUUGGUUCGUUUCCAAGGga CCUUGGAAACGAACCAAGC -3.3 -3.4 -4.3 2 1 2 -37.8 64.9 3 2 II 52.6 50.2 85.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1709 NM_022005 Huesken Fxyd6 53826 CAAGGGAACACAAUGGGCAgg UGCCCAUUGUGUUCCCUUG -2.1 -2.1 1.9 0 0 4 -39.8 44.3 -8.4 4 III 52.6 49.7 95.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1710 NM_022005 Huesken Fxyd6 53826 GGUGGGGCAGGCUCUGGUGug CACCAGAGCCUGCCCCACC -2.1 -3.3 0.8 0 1 5 -48.1 32.3 -2.4 1 II 73.7 34.5 90.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1711 NM_022005 Huesken Fxyd6 53826 GUGGGGCAGGCUCUGGUGUga ACACCAGAGCCUGCCCCAC -2.2 -2.2 0.8 1 0 5 -47 36.2 1.4 1 III 68.4 34.2 72.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1712 NM_022005 Huesken Fxyd6 53826 GUGUGAGUUUCCACUCUGGug CCAGAGUGGAAACUCACAC -3.3 -2.2 -5.9 0 1 2 -39.1 54 -7.3 3 II 52.6 46.7 95.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1713 NM_022005 Huesken Fxyd6 53826 GUGAGUUUCCACUCUGGUGac CACCAGAGUGGAAACUCAC -2.1 -2.2 -5.9 2 1 2 -39.1 68.4 -0.1 2 II 52.6 51.9 92.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1714 NM_022005 Huesken Fxyd6 53826 GUUUCCACUCUGGUGACCUuu AGGUCACCAGAGUGGAAAC -2.1 -2.2 -1.7 0 2 2 -40.3 62.2 -1.6 3 II 52.6 48.2 94.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1715 NM_022005 Huesken Fxyd6 53826 CUCUGGUGACCUUUGACUCcc GAGUCAAAGGUCACCAGAG -2.4 -2.1 0.5 0 1 2 -39.3 67.9 8.4 3 II 52.6 52.8 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1716 NM_022005 Huesken Fxyd6 53826 ACCUUUGACUCCCGUAGGCgu GCCUACGGGAGUCAAAGGU -3.4 -2.2 -3.3 1 3 4 -41.9 53.6 5.1 3 Ib 57.9 49.7 91.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1717 NM_022005 Huesken Fxyd6 53826 UUGACUCCCGUAGGCGUUUgc AAACGCCUACGGGAGUCAA -0.9 -0.9 -3.3 0 0 4 -39.8 56.5 -4 5 II 52.6 57.6 93.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1718 NM_022005 Huesken Fxyd6 53826 CACGGGUGUGCAUACCCUGuu CAGGGUAUGCACACCCGUG -2.1 -2.1 -5.6 0 0 4 -42.8 39.1 -4.4 0 II 63.2 49.9 70.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1719 NM_022005 Huesken Fxyd6 53826 GGUGUGCAUACCCUGUUGCuc GCAACAGGGUAUGCACACC -3.4 -3.3 -1.9 0 2 3 -41.4 56.6 7.4 2 II 57.9 44.8 72.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1720 NM_022005 Huesken Fxyd6 53826 CAUACCCUGUUGCUCUCUCcc GAGAGAGCAACAGGGUAUG -2.4 -2.1 1 0 2 3 -39.6 66.4 10.1 3 II 52.6 48.9 85.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1721 NM_022005 Huesken Fxyd6 53826 CCUGUUGCUCUCUCCCGCUgc AGCGGGAGAGAGCAACAGG -2.1 -3.3 -1.9 -1 -1 5 -44.1 46.1 -8.3 1 III 63.2 43.8 43.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1722 NM_022005 Huesken Fxyd6 53826 GUUGCUCUCUCCCGCUGCCcc GGCAGCGGGAGAGAGCAAC -3.3 -2.2 -1.9 0 3 5 -45.4 47.3 5.1 0 II 68.4 44 61.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1723 NM_022005 Huesken Fxyd6 53826 CUCUCUCCCGCUGCCCCUGaa CAGGGGCAGCGGGAGAGAG -2.1 -2.1 0 0 5 -47.6 45.3 -1.3 1 II 73.7 43.9 66.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1724 NM_022005 Huesken Fxyd6 53826 CACUCCGACCCCUGACAGGca CCUGUCAGGGGUCGGAGUG -3.3 -2.1 -1.9 -1 0 4 -45.3 43 -6.7 1 II 68.4 40.7 72.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1725 NM_022005 Huesken Fxyd6 53826 ACCCCUGACAGGCAGGGGAaa UCCCCUGCCUGUCAGGGGU -2.4 -2.2 -9.7 3 0 4 -48.3 38.3 -1.4 2 II 68.4 38.7 42.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1726 NM_022005 Huesken Fxyd6 53826 GGGAAAGAAACUGUAGUCUgc AGACUACAGUUUCUUUCCC -2.1 -3.3 0.2 0 -1 3 -35.8 57.6 1.7 5 III 42.1 39.9 55.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1727 NM_022005 Huesken Fxyd6 53826 AAAGAAACUGUAGUCUGCCag GGCAGACUACAGUUUCUUU -3.3 -0.9 -0.1 1 6 3 -35.6 60.8 12.4 6 Ia 42.1 71.2 86 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1728 NM_022005 Huesken Fxyd6 53826 AACUGUAGUCUGCCAGAUUcc AAUCUGGCAGACUACAGUU -0.9 -0.9 -1.7 1 0 3 -37 63.4 -1.6 4 II 42.1 52.3 81.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1729 NM_022005 Huesken Fxyd6 53826 CAGAUUCCACACCAUGUGGca CCACAUGGUGUGGAAUCUG -3.3 -2.1 -4.9 -1 0 2 -39.1 64.6 0.4 3 II 52.6 50.9 40.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1730 NM_022005 Huesken Fxyd6 53826 CACACCAUGUGGCAGAGAGac CUCUCUGCCACAUGGUGUG -2.1 -2.1 -2.4 0 0 3 -41.4 55.5 0.4 1 II 57.9 42 46.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1731 NM_022005 Huesken Fxyd6 53826 AUGUGGCAGAGAGACAGAGcc CUCUGUCUCUCUGCCACAU -2.1 -1.1 1.8 2 3 3 -40.7 47.7 0 5 II 52.6 54.2 62.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1732 NM_022005 Huesken Fxyd6 53826 GUGGCAGAGAGACAGAGCCac GGCUCUGUCUCUCUGCCAC -3.3 -2.2 -3.8 1 2 3 -44.2 41.5 9.8 1 II 63.2 50.6 45.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1733 NM_022005 Huesken Fxyd6 53826 UGGCAGAGAGACAGAGCCAcc UGGCUCUGUCUCUCUGCCA -2.1 -2.1 -3.8 0 0 3 -44.1 35.9 -3.7 3 II 57.9 49.8 76.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1734 NM_022005 Huesken Fxyd6 53826 GCAGAGAGACAGAGCCACCgg GGUGGCUCUGUCUCUCUGC -3.3 -3.4 0.5 -1 1 3 -44.2 30.2 9.8 2 II 63.2 44.3 71.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1735 NM_022005 Huesken Fxyd6 53826 CCUGCUGCCUGUCCCCUGGgc CCAGGGGACAGGCAGCAGG -3.3 -3.3 0.4 0 0 4 -48 46.5 3.4 2 II 73.7 42.3 45.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1736 NM_022005 Huesken Fxyd6 53826 CCCUGGGCUAUCUCCUGCCac GGCAGGAGAUAGCCCAGGG -3.3 -3.3 -3.4 -1 0 4 -46.4 44.1 3.1 1 II 68.4 48.3 67.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1737 NM_022005 Huesken Fxyd6 53826 CUGCCACAGACCAGCUUCAga UGAAGCUGGUCUGUGGCAG -2.1 -2.1 -2.2 0 -3 3 -42.4 38.7 -13 1 III 57.9 35.7 44.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1738 NM_022005 Huesken Fxyd6 53826 CUUCAGAGAAGGAAGGAGUcc ACUCCUUCCUUCUCUGAAG -2.2 -2.1 -0.6 0 -1 2 -38.2 52.5 -5.9 5 II 47.4 48.9 50.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1739 NM_022005 Huesken Fxyd6 53826 AGAGAAGGAAGGAGUCCUCug GAGGACUCCUUCCUUCUCU -2.4 -2.1 -3.3 0 3 2 -40.9 42.7 7.5 5 Ib 52.6 52.6 81.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1740 NM_022005 Huesken Fxyd6 53826 GCUAGAGAUGGAAGUCUCAga UGAGACUUCCAUCUCUAGC -2.1 -3.4 -2.8 -1 -2 2 -38.9 40.8 -6.3 3 III 47.4 31.3 32.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1741 NM_022005 Huesken Fxyd6 53826 GAAGUCUCAGAAGCAGGGAag UCCCUGCUUCUGAGACUUC -2.4 -2.4 1.7 1 0 3 -40.7 46.6 -1.5 4 II 52.6 38.7 67.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1742 NM_022005 Huesken Fxyd6 53826 AGGGAAGGUGGAUGAAGGCag GCCUUCAUCCACCUUCCCU -3.4 -2.1 0 3 3 -42.7 36.7 10.1 3 II 57.9 48.7 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1743 NM_022005 Huesken Fxyd6 53826 GCAGAAGGGCUCCAAAGCCua GGCUUUGGAGCCCUUCUGC -3.3 -3.4 -4.5 1 2 4 -43.5 27.1 10.2 1 II 63.2 43.6 73.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1744 NM_022005 Huesken Fxyd6 53826 GCUCCAAAGCCUAUGGGGAua UCCCCAUAGGCUUUGGAGC -2.4 -3.4 -2 2 0 4 -42.8 41.2 -3.3 0 III 57.9 27.5 35.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1745 NM_022005 Huesken Fxyd6 53826 UGGGGAUAUUGCUCAGAAGuu CUUCUGAGCAAUAUCCCCA -2.1 -2.1 1.1 1 1 4 -38.4 60.5 -2.4 4 II 47.4 55.1 93 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1746 NM_022005 Huesken Fxyd6 53826 UAUUGCUCAGAAGUUAAGUaa ACUUAACUUCUGAGCAAUA -2.2 -1.3 -0.2 1 3 2 -32.5 87.5 0.7 7 II 31.6 67.8 90.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1747 NM_022005 Huesken Fxyd6 53826 GUUAAGUAAGGAGCUCAUUcc AAUGAGCUCCUUACUUAAC -0.9 -2.2 -0.2 1 -1 2 -33.7 62.9 -1.3 5 II 36.8 45.2 70.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1748 NM_022005 Huesken Fxyd6 53826 CUCAUUCCUCAGAGGCAAGaa CUUGCCUCUGAGGAAUGAG -2.1 -2.1 -1.2 -2 -1 3 -39.3 55.3 -2.3 2 II 52.6 42.5 59.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1749 NM_022005 Huesken Fxyd6 53826 AAGAAUUCCUGGGUGUUCUgu AGAACACCCAGGAAUUCUU -2.1 -0.9 1 3 2 3 -36.7 77.9 1.1 7 II 42.1 60.9 84.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1750 NM_022005 Huesken Fxyd6 53826 UGGGUGUUCUGUAAAGGGUgg ACCCUUUACAGAACACCCA -2.2 -2.1 2 2 1 3 -38.9 63.6 -3.5 5 II 47.4 58.1 86.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1751 NM_022005 Huesken Fxyd6 53826 UAAAGGGUGGGGCGGAUUGgg CAAUCCGCCCCACCCUUUA -2.1 -1.3 4.3 0 3 7 -41.6 54.1 2.4 7 Ib 57.9 64.6 80.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1752 NM_022005 Huesken Fxyd6 53826 CCUAAGUGGGCACCCUAAAag UUUAGGGUGCCCACUUAGG -0.9 -3.3 -2.5 1 -4 4 -40.1 43.8 -3 3 II 52.6 31.1 48.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1753 NM_022005 Huesken Fxyd6 53826 AGACGCCUCAAGGGAGGCAau UGCCUCCCUUGAGGCGUCU -2.1 -2.1 -8.1 2 1 4 -45.3 33 -1.5 2 II 63.2 37.5 34.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1754 NM_022005 Huesken Fxyd6 53826 GACGCCUCAAGGGAGGCAAuc UUGCCUCCCUUGAGGCGUC -0.9 -2.4 -8.1 1 -2 4 -44.1 42.1 -3.8 1 III 63.2 29.2 37.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1755 NM_022005 Huesken Fxyd6 53826 CUGAAUCUCCAACUGCAAAcg UUUGCAGUUGGAGAUUCAG -0.9 -2.1 1.2 0 -3 2 -35.5 65.1 4 3 II 42.1 38.5 48.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1756 NM_022005 Huesken Fxyd6 53826 CUUCUAAACUGGUGGAAUCug GAUUCCACCAGUUUAGAAG -2.4 -2.1 1.6 0 0 2 -34.7 65.8 5.4 4 II 42.1 50.4 84 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1757 NM_022005 Huesken Fxyd6 53826 AAUCUGGAGCAAGUUUCUUcu AAGAAACUUGCUCCAGAUU -0.9 -0.9 1.6 3 3 2 -34.3 65.8 0.7 6 II 36.8 53.7 79 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1758 NM_022005 Huesken Fxyd6 53826 UCUGGAGCAAGUUUCUUCUca AGAAGAAACUUGCUCCAGA -2.1 -2.4 1.6 0 2 2 -36.8 78.6 1.4 7 II 42.1 62.2 90 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1759 NM_022005 Huesken Fxyd6 53826 UUUCUUCUCAGAGUCCACAag UGUGGACUCUGAGAAGAAA -2.1 -0.9 -0.7 2 2 2 -37.1 77.9 -1.4 7 II 42.1 66.9 85.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1760 NM_022005 Huesken Fxyd6 53826 UCAGAGUCCACAAGGAACAuc UGUUCCUUGUGGACUCUGA -2.1 -2.4 -2.3 1 0 2 -39.3 51.5 -6 6 II 47.4 60.7 94.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1761 NM_022005 Huesken Fxyd6 53826 GUCCACAAGGAACAUCAGUga ACUGAUGUUCCUUGUGGAC -2.2 -2.2 -2.3 2 -1 2 -38.1 49.9 3.4 2 III 47.4 41.2 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1762 NM_022005 Huesken Fxyd6 53826 ACGAACUUUCUCAGCCCCGgg CGGGGCUGAGAAAGUUCGU -2.4 -2.2 -4.1 1 3 6 -40.8 49.1 -2.2 3 Ib 57.9 59.8 95.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1763 NM_022005 Huesken Fxyd6 53826 GAACUUUCUCAGCCCCGGGau CCCGGGGCUGAGAAAGUUC -3.3 -2.4 -2.4 2 3 8 -42.8 54.2 4.7 2 II 63.2 52 85.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1764 NM_022005 Huesken Fxyd6 53826 UCUCAGCCCCGGGAUCACUgg AGUGAUCCCGGGGCUGAGA -2.1 -2.4 0.9 2 1 8 -45.7 41.4 -1.3 4 II 63.2 50.2 94.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1765 NM_022005 Huesken Fxyd6 53826 GGUACAACUCUCCCUCAAGcc CUUGAGGGAGAGUUGUACC -2.1 -3.3 0.6 0 0 3 -39.4 55.2 0.1 3 II 52.6 39.2 63.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1766 NM_022005 Huesken Fxyd6 53826 CAACUCUCCCUCAAGCCUAaa UAGGCUUGAGGGAGAGUUG -1.3 -2.1 -2.3 2 -2 3 -40.5 49.9 -10.7 3 II 52.6 46.3 76.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1767 NM_022005 Huesken Fxyd6 53826 UCUCCCUCAAGCCUAAAUCca GAUUUAGGCUUGAGGGAGA -2.4 -2.4 0.6 2 3 3 -38.5 78.9 9.8 6 II 47.4 66.6 90.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1768 NM_022005 Huesken Fxyd6 53826 UCCCUCAAGCCUAAAUCCAga UGGAUUUAGGCUUGAGGGA -2.1 -2.4 1.6 2 0 3 -39.4 56.3 -5.7 5 II 47.4 53.3 81.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1769 NM_022005 Huesken Fxyd6 53826 CCAGAAAGAGGGGACUAAGgg CUUAGUCCCCUCUUUCUGG -2.1 -3.3 0.3 -1 -1 4 -39.2 37.3 0.7 3 II 52.6 39.2 87.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1770 NM_022005 Huesken Fxyd6 53826 CUAAGGGCUCCUCAGGGACgg GUCCCUGAGGAGCCCUUAG -2.2 -2.1 -4.4 -1 1 4 -44.1 43.7 8.5 2 II 63.2 47.7 85.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1771 NM_022005 Huesken Fxyd6 53826 GGGAGACUCCAGAGAGCAAga UUGCUCUCUGGAGUCUCCC -0.9 -3.3 -3 0 -3 3 -43.1 29.3 -4 -1 III 57.9 16.6 58.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1772 NM_022005 Huesken Fxyd6 53826 ACUCCAGAGAGCAAGAGUAga UACUCUUGCUCUCUGGAGU -1.3 -2.2 -3.7 3 0 2 -39.7 48.1 -8.7 4 II 47.4 42.9 57.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1773 NM_022005 Huesken Fxyd6 53826 AGAGUAGAUGGAGGUCACAgg UGUGACCUCCAUCUACUCU -2.1 -2.1 0.8 0 0 2 -39.9 40.2 -3.8 5 II 47.4 43.4 96.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1774 NM_022005 Huesken Fxyd6 53826 AUGGAGGUCACAGGAGGGCac GCCCUCCUGUGACCUCCAU -3.4 -1.1 0.9 1 4 4 -45.2 35 7.8 5 II 63.2 57.5 89 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1775 NM_022005 Huesken Fxyd6 53826 AUGGGAGAGGAAGCACACAgu UGUGUGCUUCCUCUCCCAU -2.1 -1.1 2.5 2 0 3 -41.6 35.9 -1.5 4 II 52.6 48.3 104.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1776 NM_022005 Huesken Fxyd6 53826 CACAGUUCACAGGAACAAUga AUUGUUCCUGUGAACUGUG -1.1 -2.1 -1.9 0 -3 2 -35.4 59.2 -3.7 2 II 42.1 40.6 76.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1777 NM_022005 Huesken Fxyd6 53826 CAGUUCACAGGAACAAUGAaa UCAUUGUUCCUGUGAACUG -2.4 -2.1 -1.9 -1 -3 2 -35.6 63.3 -8.3 4 II 42.1 44.9 66.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1778 NM_022005 Huesken Fxyd6 53826 UCACAGGAACAAUGAAACGac CGUUUCAUUGUUCCUGUGA -2.4 -2.4 -0.5 0 3 2 -34.7 56.3 5 6 II 42.1 64.1 54.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1779 NM_022005 Huesken Fxyd6 53826 UGAAACGACCACGAACGACca GUCGUUCGUGGUCGUUUCA -2.2 -2.1 1 1 3 2 -38 52.6 10.1 7 Ib 52.6 60.2 39.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1780 XM_214061 Huesken TCAP 8557 UUUGUUUUCAACAUGGUAAgg UUACCAUGUUGAAAACAAA -0.9 -0.9 0.4 2 1 2 -29.4 100.8 -4.1 9 II 26.3 70.8 91.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1781 XM_214061 Huesken TCAP 8557 CAACAUGGUAAGGGUUUUGac CAAAACCCUUACCAUGUUG -2.1 -2.1 2 -1 0 3 -33.9 59.1 3 6 II 42.1 50.9 70.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1782 XM_214061 Huesken TCAP 8557 CAUGGUAAGGGUUUUGACCuc GGUCAAAACCCUUACCAUG -3.3 -2.1 -0.9 0 2 3 -36.6 72.9 10.8 3 II 47.4 60.1 84.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1783 XM_214061 Huesken TCAP 8557 AUGGUAAGGGUUUUGACCUca AGGUCAAAACCCUUACCAU -2.1 -1.1 -1.1 2 3 3 -36.6 70 1.4 4 II 42.1 63.9 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1784 XM_214061 Huesken TCAP 8557 CCUCAAAUGCUUAUCAGGUcu ACCUGAUAAGCAUUUGAGG -2.2 -3.3 0.1 1 0 2 -35.8 57.2 -0.5 3 II 42.1 43.2 46.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1785 XM_214061 Huesken TCAP 8557 CGCCUCUUCCUUGAAGUUUug AAACUUCAAGGAAGAGGCG -0.9 -2.4 -2.1 2 -4 4 -36.8 58.3 -3 2 III 47.4 37.9 66.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1786 XM_214061 Huesken TCAP 8557 AUUGCAGGUUUUCCUUCUCag GAGAAGGAAAACCUGCAAU -2.4 -1.1 -1.4 1 4 2 -35.5 70.6 12.8 4 Ib 42.1 60.5 79.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1787 XM_214061 Huesken TCAP 8557 ACACAAAGGGUAUUGCAAGga CUUGCAAUACCCUUUGUGU -2.1 -2.2 -1.6 3 3 3 -35.2 55.1 5 4 Ia 42.1 54.4 74.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1788 XM_214061 Huesken TCAP 8557 CAAAGGGUAUUGCAAGGAUcu AUCCUUGCAAUACCCUUUG -1.1 -2.1 1.1 -1 -1 3 -35.5 50.3 -3.6 4 III 42.1 40.1 66.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1789 XM_214061 Huesken TCAP 8557 CCUCAAAUAUAUGGGGAUAcc UAUCCCCAUAUAUUUGAGG -1.3 -3.3 0.8 -1 -4 4 -34.4 52.9 2.3 3 II 36.8 27.6 48.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1790 XM_214061 Huesken TCAP 8557 UCAAAUAUAUGGGGAUACCaa GGUAUCCCCAUAUAUUUGA -3.3 -2.4 -0.4 -1 3 4 -34.5 70.8 10.1 7 Ia 36.8 67.1 76.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1791 XM_214061 Huesken TCAP 8557 CAACUUGUACAGACGAACAag UGUUCGUCUGUACAAGUUG -2.1 -2.1 0.2 0 -2 2 -34.8 63.7 -6 4 II 42.1 49.5 84.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1792 XM_214061 Huesken TCAP 8557 AACUUGUACAGACGAACAAga UUGUUCGUCUGUACAAGUU -0.9 -0.9 -0.7 2 0 2 -33.6 67.7 -1.4 7 II 36.8 48.3 55.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1793 XM_214061 Huesken TCAP 8557 ACUUGUACAGACGAACAAGac CUUGUUCGUCUGUACAAGU -2.1 -2.2 -3.1 1 2 2 -34.8 62.2 -0.1 4 Ia 42.1 54.2 54.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1794 XM_214061 Huesken TCAP 8557 UACAGACGAACAAGACCUCau GAGGUCUUGUUCGUCUGUA -2.4 -1.3 0.4 -1 3 2 -37.7 52.6 2.5 6 Ib 47.4 61.1 72.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1795 XM_214061 Huesken TCAP 8557 GACCUCAUCUCCCAUACCGgg CGGUAUGGGAGAUGAGGUC -2.4 -2.4 1.6 2 2 3 -41.5 56.4 -2.3 2 II 57.9 50.6 84.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1796 XM_214061 Huesken TCAP 8557 UCUCCCAUACCGGGUUCCGuu CGGAACCCGGUAUGGGAGA -2.4 -2.4 -3.7 0 4 5 -43.7 50.4 -2.4 3 II 63.2 56.1 49.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1797 XM_214061 Huesken TCAP 8557 AAAAUGAGUUAGGCUGUCCca GGACAGCCUAACUCAUUUU -3.3 -0.9 -0.2 1 4 3 -35.7 72.2 9.7 8 Ia 42.1 70 62.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1798 XM_214061 Huesken TCAP 8557 CAAACUCAUCAGGCAGGUUau AACCUGCCUGAUGAGUUUG -0.9 -2.1 1.9 -1 -1 3 -37.7 54.3 -3.7 3 II 47.4 40.1 52 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1799 XM_214061 Huesken TCAP 8557 GCAGGUUAUAAUAGAUAGUgu ACUAUCUAUUAUAACCUGC -2.2 -3.4 2.8 0 -1 2 -32.2 64.2 -1.2 3 III 31.6 43.4 42.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1800 XM_214061 Huesken TCAP 8557 AGUGUAGCACAUAAAAUUUaa AAAUUUUAUGUGCUACACU -0.9 -2.1 0.2 1 0 2 -29.8 75 -1.2 6 II 26.3 52.8 46.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1801 XM_214061 Huesken TCAP 8557 AUACAUCUCUCCUCCUUUGgu CAAAGGAGGAGAGAUGUAU -2.1 -1.1 3.7 3 3 2 -36.3 75 -2 6 Ia 42.1 62.8 99.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1802 XM_214061 Huesken TCAP 8557 UCCUCCUUUGGUCUCACACag GUGUGAGACCAAAGGAGGA -2.2 -2.4 -1 1 3 2 -40.5 81.2 15.2 4 II 52.6 61.8 98 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1803 XM_214061 Huesken TCAP 8557 AGAAACAAUACAAUCCUCCga GGAGGAUUGUAUUGUUUCU -3.3 -2.1 0.5 1 4 2 -33.7 74.9 7.5 8 Ia 36.8 73.8 104.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1804 XM_214061 Huesken TCAP 8557 AAACAAUACAAUCCUCCGAcc UCGGAGGAUUGUAUUGUUU -2.4 -0.9 1.5 4 2 3 -34 72.6 6.7 7 II 36.8 58.3 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1805 XM_214061 Huesken TCAP 8557 UCCGACCCUUCUCCCAGGUca ACCUGGGAGAAGGGUCGGA -2.2 -2.4 -3.2 0 1 3 -45.5 47.4 1.8 2 II 63.2 45.8 77.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1806 XM_214061 Huesken TCAP 8557 CCCUUCUCCCAGGUCAUCAgu UGAUGACCUGGGAGAAGGG -2.1 -3.3 -3.2 1 -3 3 -42.9 59 -1.1 2 III 57.9 38.5 33.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1807 XM_214061 Huesken TCAP 8557 GUCCUAGCCGUGUAAGGCCca GGCCUUACACGGCUAGGAC -3.3 -2.2 -5 2 2 4 -43.3 43.6 7.4 1 II 63.2 49.2 60 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1808 XM_214061 Huesken TCAP 8557 AUUGCUGCAUGGAGUCCUCuu GAGGACUCCAUGCAGCAAU -2.4 -1.1 0.5 0 4 2 -40.6 58 4.8 5 Ib 52.6 57.4 44.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1809 XM_214061 Huesken TCAP 8557 GGUGAGCUCCAACUCCAAGuc CUUGGAGUUGGAGCUCACC -2.1 -3.3 -3.7 1 1 2 -41.4 47.5 9.7 0 II 57.9 36.3 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1810 XM_214061 Huesken TCAP 8557 UCCAACUCCAAGUCUCAGUgu ACUGAGACUUGGAGUUGGA -2.2 -2.4 -0.1 2 0 2 -39.3 75.9 1 7 II 47.4 60.6 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1811 XM_214061 Huesken TCAP 8557 AAGUCUCAGUGUCACAGGGac CCCUGUGACACUGAGACUU -3.3 -0.9 2.2 2 4 3 -40.3 65.5 5.4 4 Ib 52.6 56.6 65.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1812 XM_214061 Huesken TCAP 8557 GUCUCAGUGUCACAGGGACcc GUCCCUGUGACACUGAGAC -2.2 -2.2 -1.5 1 1 3 -41.9 47.8 7.5 1 II 57.9 36.8 43 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1813 XM_214061 Huesken TCAP 8557 AGUGUCACAGGGACCCAAAgu UUUGGGUCCCUGUGACACU -0.9 -2.1 -1.5 1 -1 3 -41.2 52 -6.3 4 II 52.6 42 50.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1814 XM_214061 Huesken TCAP 8557 GUCACAGGGACCCAAAGUUca AACUUUGGGUCCCUGUGAC -0.9 -2.2 0.2 1 -1 3 -40 46.4 -6.3 4 III 52.6 37.9 26.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1815 XM_214061 Huesken TCAP 8557 GCACCUCAAAUUCAGGAACac GUUCCUGAAUUUGAGGUGC -2.2 -3.4 -0.9 1 0 2 -36.8 57.8 12.8 2 II 47.4 41.2 23.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1816 XM_214061 Huesken TCAP 8557 CUCAAAUUCAGGAACACACca GUGUGUUCCUGAAUUUGAG -2.2 -2.1 1.9 1 0 2 -34.4 69.6 5.5 5 II 42.1 58 32.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1817 XM_214061 Huesken TCAP 8557 CCAGGAAUGAACGUUAUUCac GAAUAACGUUCAUUCCUGG -2.4 -3.3 -0.2 0 0 2 -34 61.6 7.7 4 II 42.1 52.4 66.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1818 XM_214061 Huesken TCAP 8557 AUGUGAGCGCAUUUUCCAAau UUGGAAAAUGCGCUCACAU -0.9 -1.1 1 2 1 4 -35.8 68.6 3.9 5 II 42.1 45.6 38.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1819 XM_214061 Huesken TCAP 8557 UGUGAGCGCAUUUUCCAAAuc UUUGGAAAAUGCGCUCACA -0.9 -2.1 1 1 0 4 -35.6 68.7 4.3 6 II 42.1 52.4 47.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1820 XM_214061 Huesken TCAP 8557 CAUUUUCCAAAUCAAAGUUau AACUUUGAUUUGGAAAAUG -0.9 -2.1 1.4 -1 -1 2 -28.1 87.9 1.8 5 II 26.3 50.1 50.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1821 XM_214061 Huesken TCAP 8557 UUCCAAAUCAAAGUUAUUUuc AAAUAACUUUGAUUUGGAA -0.9 -0.9 1.4 2 1 2 -27.3 90.4 3.4 8 II 21.1 69.3 70.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1822 XM_214061 Huesken TCAP 8557 UCCAAAUCAAAGUUAUUUUcc AAAAUAACUUUGAUUUGGA -0.9 -2.4 1.4 1 0 2 -27.3 96 3.4 8 II 21.1 61.9 69.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1823 XM_214061 Huesken TCAP 8557 AAACUCAUAUCGAGGUCGUca ACGACCUCGAUAUGAGUUU -2.2 -0.9 -0.9 1 3 2 -35.9 61.1 -8.9 6 II 42.1 53.3 70 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1824 XM_214061 Huesken TCAP 8557 AGACCAUAGCAGAAACGUAgu UACGUUUCUGCUAUGGUCU -1.3 -2.1 0.5 4 0 2 -36.5 49.8 -4 4 II 42.1 43.5 62.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1825 XM_214061 Huesken TCAP 8557 GAAGACAGAGGGGAAAAGAaa UCUUUUCCCCUCUGUCUUC -2.4 -2.4 0 -1 4 -38.2 42 -1.1 4 II 47.4 38.6 35.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1826 XM_214061 Huesken TCAP 8557 GAAAACAAAGGCUCUCUGGuu CCAGAGAGCCUUUGUUUUC -3.3 -2.4 -2.8 0 2 3 -36.5 66.7 0.4 5 II 47.4 54.1 89.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1827 XM_214061 Huesken TCAP 8557 AAGGCUCUCUGGUUUCAGCuu GCUGAAACCAGAGAGCCUU -3.4 -0.9 -1.4 2 4 3 -40.2 72.3 9.7 2 II 52.6 59.3 102 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1828 XM_214061 Huesken TCAP 8557 UUUCAGCUUCUCCAGGGUGuc CACCCUGGAGAAGCUGAAA -2.1 -0.9 1.4 1 4 3 -40.1 58.3 2.8 6 Ib 52.6 64.9 66.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1829 XM_214061 Huesken TCAP 8557 AGGGUGUCAUGUCAGCCAAuc UUGGCUGACAUGACACCCU -0.9 -2.1 0.8 2 -1 3 -41.4 52.8 1.7 4 II 52.6 39.6 65.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1830 XM_214061 Huesken TCAP 8557 UCGCCAUCACUCAACCAGAau UCUGGUUGAGUGAUGGCGA -2.4 -2.4 0.5 2 -1 4 -41 49 -8.7 4 II 52.6 52.5 75.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1831 XM_214061 Huesken TCAP 8557 UGGAAACCGCGGACGGCUCac GAGCCGUCCGCGGUUUCCA -2.4 -2.1 -6.3 1 2 6 -44.8 41.5 7.5 3 Ib 68.4 53.6 70.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1832 XM_214061 Huesken TCAP 8557 GAAACCGCGGACGGCUCACga GUGAGCCGUCCGCGGUUUC -2.2 -2.4 -6.5 0 2 6 -43.7 37.7 7.4 2 II 68.4 40.1 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1833 XM_214061 Huesken TCAP 8557 CGCGGACGGCUCACGAAGAcu UCUUCGUGAGCCGUCCGCG -2.4 -2.4 -2 0 -4 5 -44.2 19.5 -10.7 -2 III 68.4 24 35.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1834 XM_214061 Huesken TCAP 8557 AUCCGCCGCACGAGCUGCAcc UGCAGCUCGUGCGGCGGAU -2.1 -1.1 -1.9 2 1 7 -46 32.3 -8.7 2 II 68.4 41.1 33.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1835 XM_214061 Huesken TCAP 8557 CGAGCUGCACCAGCAUCUCgg GAGAUGCUGGUGCAGCUCG -2.4 -2.4 -3.1 -1 0 2 -43.2 37.2 3.1 0 II 63.2 42.5 32.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1836 XM_214061 Huesken TCAP 8557 CCAGCAUCUCGGCCAUCUUcg AAGAUGGCCGAGAUGCUGG -0.9 -3.3 -1.3 0 -2 5 -42 43.9 -3.6 0 III 57.9 34 33.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1837 XM_214061 Huesken TCAP 8557 GGCCAUCUUCGCCAUCUCCug GGAGAUGGCGAAGAUGGCC -3.3 -3.3 -2.4 1 0 4 -43.5 48.4 10.2 0 II 63.2 40.7 72.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1838 XM_214061 Huesken TCAP 8557 CCAUCUUCGCCAUCUCCUGcg CAGGAGAUGGCGAAGAUGG -2.1 -3.3 1.1 1 0 4 -41 57 -4.4 2 II 57.9 47.1 81.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1839 XM_214061 Huesken TCAP 8557 CGCCCUGCAGGUGGUUGAGag CUCAACCACCUGCAGGGCG -2.1 -2.4 -1.2 -1 -1 5 -44.8 36.7 1 -1 II 68.4 27.2 43.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1840 XM_214061 Huesken TCAP 8557 GAGAGCGCUCUCCUCAGAGgc CUCUGAGGAGAGCGCUCUC -2.1 -2.4 -2.5 0 2 4 -43.7 46 2.4 1 II 63.2 43.3 48.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1841 XM_214061 Huesken TCAP 8557 GCUCUCCUCAGAGGCCUCUac AGAGGCCUCUGAGGAGAGC -2.1 -3.4 -2.4 1 -1 4 -45.5 40.8 -4 2 III 63.2 32.5 69.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1842 XM_214061 Huesken TCAP 8557 ACCUGCGUCUUGAUCUGGAuc UCCAGAUCAAGACGCAGGU -2.4 -2.2 1.3 2 1 3 -41 52.6 -4 4 II 52.6 41.1 54.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1843 XM_214061 Huesken TCAP 8557 CAUAUUGUCCAUCUCCCACag GUGGGAGAUGGACAAUAUG -2.2 -2.1 1.4 0 2 3 -37.5 80.3 15.5 5 II 47.4 57 79.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1844 XM_214061 Huesken TCAP 8557 UCUCCCACAGCUUGCCCCGgu CGGGGCAAGCUGUGGGAGA -2.4 -2.4 -0.1 0 4 6 -46.2 52.8 0.7 4 II 68.4 60.8 69.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1845 XM_214061 Huesken TCAP 8557 CUCCCACAGCUUGCCCCGGuu CCGGGGCAAGCUGUGGGAG -3.3 -2.1 -0.4 1 1 7 -47.1 30.5 1 0 II 73.7 39.9 44.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1846 XM_214061 Huesken TCAP 8557 GCGCACGGGCGCGCGUCCGcg CGGACGCGCGCCCGUGCGC -2.4 -3.4 -7 2 1 10 -50.2 12.2 0.4 0 II 89.5 31.4 19.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1847 XM_214061 Huesken TCAP 8557 CGCGCUCGCGCGUCAGCGAcg UCGCUGACGCGCGAGCGCG -2.4 -2.4 -5.8 0 -3 6 -47.1 25.2 -8.1 -2 III 78.9 23.7 14 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1848 XM_214061 Huesken TCAP 8557 UCUCGUGGAUGACGGGCAGca CUGCCCGUCAUCCACGAGA -2.1 -2.4 -0.5 0 3 5 -43.7 40.8 2.4 4 II 63.2 47.3 70.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1849 XM_214061 Huesken TCAP 8557 AUGACGGGCAGCAGAAACUgc AGUUUCUGCUGCCCGUCAU -2.1 -1.1 0 1 1 5 -40.5 52.2 -8.9 6 II 52.6 57.5 66.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1850 XM_214061 Huesken TCAP 8557 AGCAGAAACUGCUCGAAGUcc ACUUCGAGCAGUUUCUGCU -2.2 -2.1 -3.9 2 0 2 -38.2 59.6 -6.3 3 II 47.4 47.1 51.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1851 XM_214061 Huesken TCAP 8557 AGCACCUCCACCUCCUCGGgc CCGAGGAGGUGGAGGUGCU -3.3 -2.1 -0.7 3 3 3 -46.5 60.5 -4.7 4 II 68.4 57.5 58.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1852 XM_214061 Huesken TCAP 8557 GCCGCAUCUCCGCUGCUUUgc AAAGCAGCGGAGAUGCGGC -0.9 -3.4 -2.6 1 -2 5 -43.2 44.4 -1.6 0 III 63.2 28.6 35.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1853 XM_214061 Huesken TCAP 8557 CGCAUCUCCGCUGCUUUGCuu GCAAAGCAGCGGAGAUGCG -3.4 -2.4 -2.6 1 -1 4 -42 59.8 6.1 2 II 63.2 46.4 74.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1854 XM_214061 Huesken TCAP 8557 UCUCCGCUGCUUUGCUUGUcu ACAAGCAAAGCAGCGGAGA -2.2 -2.4 -1.4 1 1 4 -40.3 60.5 -1 4 II 52.6 49 62.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1855 XM_214061 Huesken TCAP 8557 UAUUAACAUGUAAGAUUUUgu AAAAUCUUACAUGUUAAUA -0.9 -1.3 2.6 -1 1 1 -25.7 80.2 -3.9 8 II 15.8 60.6 76.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1856 XM_214061 Huesken TCAP 8557 UAAGGGUUUUGACCUCAAAug UUUGAGGUCAAAACCCUUA -0.9 -1.3 -2.5 1 0 3 -34.2 68.6 -1.4 5 II 36.8 56.6 82.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1857 XM_214061 Huesken TCAP 8557 ACAUUUAUAGCUUGACUACau GUAGUCAAGCUAUAAAUGU -2.2 -2.2 -1.6 0 2 2 -31.7 83.3 8.1 6 Ia 31.6 58.7 88.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1858 XM_214061 Huesken TCAP 8557 UAUAGCUUGACUACAUAUGaa CAUAUGUAGUCAAGCUAUA -2.1 -1.3 -2.2 2 3 2 -32.2 91.5 -1.9 7 Ia 31.6 76.1 101.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1859 XM_214061 Huesken TCAP 8557 UUGACUACAUAUGAACCUUga AAGGUUCAUAUGUAGUCAA -0.9 -0.9 1.4 0 1 2 -32.7 81.4 1.4 6 II 31.6 66.3 85.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1860 XM_214061 Huesken TCAP 8557 GACGCCUCUUCCUUGAAGUuu ACUUCAAGGAAGAGGCGUC -2.2 -2.4 -2.1 1 0 4 -39.6 64.1 -6.3 1 III 52.6 41.2 82.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1861 XM_214061 Huesken TCAP 8557 GUUUUGGGUCCAUUGCAGGuu CCUGCAAUGGACCCAAAAC -3.3 -2.2 -1 0 3 3 -38.6 62.3 0 4 II 52.6 51.5 86.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1862 XM_214061 Huesken TCAP 8557 GGUAUUGCAAGGAUCUUUCau GAAAGAUCCUUGCAAUACC -2.4 -3.3 2.1 0 1 2 -34.9 78 7.1 6 II 42.1 52.9 82.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1863 XM_214061 Huesken TCAP 8557 AUAUGGGGAUACCAACUUGua CAAGUUGGUAUCCCCAUAU -2.1 -1.1 -1.1 1 3 4 -36.1 62.9 2.4 6 Ib 42.1 61.3 62.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1864 XM_214061 Huesken TCAP 8557 GAGUUAGGCUGUCCCAACAaa UGUUGGGACAGCCUAACUC -2.1 -2.4 -6.4 1 -2 3 -40.4 57.1 1.7 3 II 52.6 38 85.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1865 XM_214061 Huesken TCAP 8557 AUCAGGCAGGUUAUAAUAGau CUAUUAUAACCUGCCUGAU -2.1 -1.1 3 2 3 3 -34.1 68.7 2.8 5 II 36.8 58.8 88 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1866 XM_214061 Huesken TCAP 8557 GGCAGGUUAUAAUAGAUAGug CUAUCUAUUAUAACCUGCC -2.1 -3.3 2.8 1 -1 3 -33.3 70.3 2.3 3 II 36.8 42.6 90.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1867 XM_214061 Huesken TCAP 8557 CAUAGAAACAAUACAAUCCuc GGAUUGUAUUGUUUCUAUG -3.3 -2.1 0.7 0 1 2 -30.4 82.7 8.1 6 II 31.6 67.3 93.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1868 XM_214061 Huesken TCAP 8557 UCCCAGGUCAUCAGUCCUAgc UAGGACUGAUGACCUGGGA -1.3 -2.4 -2.2 1 -1 3 -42.2 43.5 -6 5 II 52.6 49 70.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1869 XM_214061 Huesken TCAP 8557 CCCAGGUCAUCAGUCCUAGcc CUAGGACUGAUGACCUGGG -2.1 -3.3 -5.3 0 -1 3 -41.9 45.2 -2 1 II 57.9 38.3 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1870 XM_214061 Huesken TCAP 8557 CAUCAGUCCUAGCCGUGUAag UACACGGCUAGGACUGAUG -1.3 -2.1 -0.8 2 -2 4 -40.1 54 1.7 4 II 52.6 37.1 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1871 XM_214061 Huesken TCAP 8557 CACAGUCCCAGAUGAAGUCug GACUUCAUCUGGGACUGUG -2.4 -2.1 0.7 -1 0 3 -39.5 56 5.4 3 II 52.6 47.2 82.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1872 XM_214061 Huesken TCAP 8557 UUCUUCUGCCAUUGCUGCAug UGCAGCAAUGGCAGAAGAA -2.1 -0.9 -1.3 1 1 3 -38.9 79.4 1.6 6 II 47.4 59.3 72.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1873 XM_214061 Huesken TCAP 8557 CUUCUGCCAUUGCUGCAUGga CAUGCAGCAAUGGCAGAAG -2.1 -2.1 -1.6 0 1 3 -38.8 57.2 2.7 2 II 52.6 47 79.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1874 XM_214061 Huesken TCAP 8557 UGCAUGGAGUCCUCUUCUAga UAGAAGAGGACUCCAUGCA -1.3 -2.1 0.5 1 -1 2 -39.8 61 -8.5 6 II 47.4 48.1 68.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1875 XM_214061 Huesken TCAP 8557 GAACUUUCAGAGGCGGUGAgc UCACCGCCUCUGAAAGUUC -2.4 -2.4 0.9 2 -1 5 -39.6 56.2 -1.5 5 II 52.6 41.6 45.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1876 XM_214061 Huesken TCAP 8557 GGCGGUGAGCUCCAACUCCaa GGAGUUGGAGCUCACCGCC -3.3 -3.3 -3.7 1 0 5 -45.4 32 7.5 0 II 68.4 42.7 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1877 XM_214061 Huesken TCAP 8557 CUCCAACUCCAAGUCUCAGug CUGAGACUUGGAGUUGGAG -2.1 -2.1 -0.1 1 1 2 -39.2 50.9 5.3 2 II 52.6 40.8 81.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1878 XM_214061 Huesken TCAP 8557 CCAACUCCAAGUCUCAGUGuc CACUGAGACUUGGAGUUGG -2.1 -3.3 -0.1 -1 1 2 -39 66.6 5.8 3 II 52.6 47.7 77.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1879 XM_214061 Huesken TCAP 8557 GGGACCCAAAGUUCAGGGAgc UCCCUGAACUUUGGGUCCC -2.4 -3.3 -3.7 0 -2 3 -42.5 50.9 -0.7 0 III 57.9 26.1 53.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1880 XM_214061 Huesken TCAP 8557 GUUCAGGGAGCUAUCAGGUca ACCUGAUAGCUCCCUGAAC -2.2 -2.2 1.2 1 2 3 -40.8 49.4 -0.9 4 III 52.6 43.7 68.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1881 XM_214061 Huesken TCAP 8557 GGGAGCUAUCAGGUCACCCaa GGGUGACCUGAUAGCUCCC -3.3 -3.3 -4.3 1 2 3 -44.4 48.9 12 0 II 63.2 48.5 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1882 XM_214061 Huesken TCAP 8557 GCUAUCAGGUCACCCAAGAaa UCUUGGGUGACCUGAUAGC -2.4 -3.4 -4.3 1 -2 3 -40.8 47.9 -3.7 3 II 52.6 32.8 45.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1883 XM_214061 Huesken TCAP 8557 AGGUCACCCAAGAAAGAGCaa GCUCUUUCUUGGGUGACCU -3.4 -2.1 -4.3 2 2 3 -40.2 57.5 7.1 3 II 52.6 54.4 95.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1884 XM_214061 Huesken TCAP 8557 GAACACACCAAAGCCAGGAau UCCUGGCUUUGGUGUGUUC -2.4 -2.4 -0.1 2 0 3 -40 46.7 1.3 5 II 52.6 43.3 66.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1885 XM_214061 Huesken TCAP 8557 ACACCAAAGCCAGGAAUGAac UCAUUCCUGGCUUUGGUGU -2.4 -2.2 -0.1 2 0 3 -38.9 36.5 -6.1 5 II 47.4 38.5 52.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1886 XM_214061 Huesken TCAP 8557 GUAUGUGAGCGCAUUUUCCaa GGAAAAUGCGCUCACAUAC -3.3 -2.2 0.6 1 3 4 -36.3 68.3 4.8 5 II 47.4 57.5 86.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1887 XM_214061 Huesken TCAP 8557 AGCGCAUUUUCCAAAUCAAag UUGAUUUGGAAAAUGCGCU -0.9 -2.1 1.5 2 -1 4 -33.3 59.1 -11 3 II 36.8 39.4 68.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1888 XM_214061 Huesken TCAP 8557 CCAUAGCAGAAACGUAGUGuc CACUACGUUUCUGCUAUGG -2.1 -3.3 0.5 -1 0 2 -36.2 47.4 5.4 4 II 47.4 40.7 58 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1889 XM_214061 Huesken TCAP 8557 AGCAGAAACGUAGUGUCAGug CUGACACUACGUUUCUGCU -2.1 -2.1 0.8 2 3 2 -37.2 52.8 2.3 4 Ib 47.4 51.2 99.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1890 XM_214061 Huesken TCAP 8557 AACGUAGUGUCAGUGAGAAca UUCUCACUGACACUACGUU -0.9 -0.9 0.9 2 1 2 -36.3 54.1 -3.8 5 II 42.1 40.9 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1891 XM_214061 Huesken TCAP 8557 CGUAGUGUCAGUGAGAACAga UGUUCUCACUGACACUACG -2.1 -2.4 -0.2 0 -3 2 -37.5 61.4 -2.7 4 III 47.4 44.9 68.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1892 XM_214061 Huesken TCAP 8557 CAGAGUGAAGACAGAGGGGaa CCCCUCUGUCUUCACUCUG -3.3 -2.1 1.9 -2 1 4 -41.6 40.8 -4.6 2 II 57.9 47.1 87.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1893 XM_214061 Huesken TCAP 8557 AAGGAAAACAAAGGCUCUCug GAGAGCCUUUGUUUUCCUU -2.4 -0.9 -3.4 1 3 3 -35.3 55.9 12.4 5 Ia 42.1 62.2 106.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1894 XM_214061 Huesken TCAP 8557 ACAAAGGCUCUCUGGUUUCag GAAACCAGAGAGCCUUUGU -2.4 -2.2 -1.3 0 2 3 -37.8 57 7.8 6 Ib 47.4 56.6 86 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1895 XM_214061 Huesken TCAP 8557 UCAGCCAAUCGCCAUCACUca AGUGAUGGCGAUUGGCUGA -2.1 -2.4 -1.9 0 1 4 -40.9 57.6 -3.9 4 II 52.6 59.5 85.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1896 XM_214061 Huesken TCAP 8557 UUCUCUAUCCGCCGCACGAgc UCGUGCGGCGGAUAGAGAA -2.4 -0.9 -0.8 0 1 7 -42 63.8 -3.7 5 II 57.9 56.8 87.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1897 XM_214061 Huesken TCAP 8557 UCUAUCCGCCGCACGAGCUgc AGCUCGUGCGGCGGAUAGA -2.1 -2.4 -1.9 1 2 7 -44.2 54.7 -8.9 4 II 63.2 54.7 79.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1898 XM_214061 Huesken TCAP 8557 CCGCCGCACGAGCUGCACCag GGUGCAGCUCGUGCGGCGG -3.3 -3.3 -2.3 1 0 7 -48 32.4 12.4 -2 II 78.9 40.2 88.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1899 XM_214061 Huesken TCAP 8557 UCUCGGCCAUCUUCGCCAUcu AUGGCGAAGAUGGCCGAGA -1.1 -2.4 -4.4 1 1 5 -42.6 51.4 -3.3 2 II 57.9 43 78.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1900 XM_214061 Huesken TCAP 8557 GCGCCUUCUCGUCGGCCUUcu AAGGCCGACGAGAAGGCGC -0.9 -3.4 -5 1 -2 5 -44.8 39.2 1.5 -1 III 68.4 27.5 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1901 XM_214061 Huesken TCAP 8557 CGUCGGCCUUCUCCGCCCUgg AGGGCGGAGAAGGCCGACG -2.1 -2.4 -4.1 0 -1 6 -47.1 31.1 -2.9 -1 III 73.7 31.3 23.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1902 XM_214061 Huesken TCAP 8557 CGGCCUUCUCCGCCCUGGGgc CCCAGGGCGGAGAAGGCCG -3.3 -2.4 -4.1 1 0 6 -48.8 37 -2 -1 II 78.9 40 65.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1903 XM_214061 Huesken TCAP 8557 GCGGGGCUCGGCGCCGCCCgc GGGCGGCGCCGAGCCCCGC -3.3 -3.4 -7.4 1 1 11 -54.2 9.4 5.1 -2 II 94.7 34.9 74.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1904 XM_214061 Huesken TCAP 8557 GCCGCCCGCGCCCUGCAGGug CCUGCAGGGCGCGGGCGGC -3.3 -3.4 -6.5 1 1 13 -52.4 22.1 0 -2 II 89.5 28.8 60.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1905 XM_214061 Huesken TCAP 8557 GGCCUCUACCUGCGUCUUGau CAAGACGCAGGUAGAGGCC -2.1 -3.3 -1 2 -1 4 -43.1 44 2.4 1 II 63.2 34.9 73.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1906 XM_214061 Huesken TCAP 8557 CUCUACCUGCGUCUUGAUCug GAUCAAGACGCAGGUAGAG -2.4 -2.1 0.6 0 0 3 -39 68.7 15.9 3 II 52.6 44.5 72 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1907 XM_214061 Huesken TCAP 8557 UGGAUCAGCAUAUUGUCCAuc UGGACAAUAUGCUGAUCCA -2.1 -2.1 -0.9 1 1 2 -37.5 76.8 -1.4 7 II 42.1 65 91.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1908 XM_214061 Huesken TCAP 8557 UAUUGUCCAUCUCCCACAGcu CUGUGGGAGAUGGACAAUA -2.1 -1.3 0.6 0 4 3 -38.5 76.3 3.1 6 Ia 47.4 62.5 82.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1909 XM_214061 Huesken TCAP 8557 CCAUCUCCCACAGCUUGCCcc GGCAAGCUGUGGGAGAUGG -3.3 -3.3 0.7 0 1 3 -43.7 50.4 3.1 2 II 63.2 47.4 81 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1910 XM_214061 Huesken TCAP 8557 CCCGGUUGCGCACGGGCGCgc GCGCCCGUGCGCAACCGGG -3.4 -3.3 -6.1 0 0 7 -49.2 19.4 5.5 -1 II 84.2 37.3 55.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1911 XM_214061 Huesken TCAP 8557 UCAGCGACGCGAUGUCCUCgc GAGGACAUCGCGUCGCUGA -2.4 -2.4 -2.2 0 3 4 -43.2 45.1 7.4 3 II 63.2 58.6 77.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1912 XM_214061 Huesken TCAP 8557 CGUGGAUGACGGGCAGCAGaa CUGCUGCCCGUCAUCCACG -2.1 -2.4 0.6 0 0 5 -44.4 29.8 -2 1 II 68.4 32.2 39.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1913 XM_214061 Huesken TCAP 8557 GUGGAUGACGGGCAGCAGAaa UCUGCUGCCCGUCAUCCAC -2.4 -2.2 1.9 1 -2 5 -44.4 36 1.4 2 III 63.2 37 35.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1914 XM_214061 Huesken TCAP 8557 CAGCAGAAACUGCUCGAAGuc CUUCGAGCAGUUUCUGCUG -2.1 -2.1 -4.6 0 0 2 -38.1 48.8 5.4 2 II 52.6 46.5 59.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1915 XM_214061 Huesken TCAP 8557 UCCGGCUCCAGCACCUCCAcc UGGAGGUGCUGGAGCCGGA -2.1 -2.4 -3.1 2 0 5 -47.7 47.3 -8.7 3 II 68.4 54.8 69.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1916 XM_214061 Huesken TCAP 8557 UCCGCCAGCUCCACUGCGUcc ACGCAGUGGAGCUGGCGGA -2.2 -2.4 -2.5 1 1 5 -46.7 42.2 -11.3 2 II 68.4 48.9 76.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1917 XM_214061 Huesken TCAP 8557 CCGCCAGCUCCACUGCGUCca GACGCAGUGGAGCUGGCGG -2.4 -3.3 -2.5 0 0 5 -46.7 29.7 7.8 -1 II 73.7 35.8 65.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1918 XM_214061 Huesken TCAP 8557 GGCCGCAUCUCCGCUGCUUug AAGCAGCGGAGAUGCGGCC -0.9 -3.3 -2.6 2 -2 6 -45.6 31.1 -8.7 -1 III 68.4 25.4 42.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1919 XM_214061 Huesken TCAP 8557 GCUUUGCUUGUCUGCACGAca UCGUGCAGACAAGCAAAGC -2.4 -3.4 -2.1 -1 -1 2 -39.2 48.5 -6.1 2 III 52.6 31.4 67.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1920 XM_214061 Huesken TCAP 8557 GCUUGUCUGCACGACACUCag GAGUGUCGUGCAGACAAGC -2.4 -3.4 -3.8 1 1 2 -40.8 48.3 7.4 0 II 57.9 41.1 64.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1921 XM_214061 Huesken TCAP 8557 GACCGAGCUCGGGCCGAGUcu ACUCGGCCCGAGCUCGGUC -2.2 -2.4 -3.1 1 -1 7 -47.5 23.6 -4 0 III 73.7 28.8 61.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1922 XM_214061 Huesken TCAP 8557 GUCUUCAAAACUUCCGCCGcu CGGCGGAAGUUUUGAAGAC -2.4 -2.2 -2.5 0 2 6 -37.2 72 0.7 4 II 52.6 56.3 94.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1923 XM_214061 Huesken TCAP 8557 AAAACUUCCGCCGCUGUUCca GAACAGCGGCGGAAGUUUU -2.4 -0.9 -2.5 3 3 7 -38.2 70.4 2.7 6 Ia 52.6 67.2 84.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1924 NM_017346 Huesken Cacnb1 782 CUGCCUCUCAGCGGAUGUAga UACAUCCGCUGAGAGGCAG -1.3 -2.1 -5.2 0 -3 4 -42.3 42.7 -8.1 0 III 57.9 30.8 39.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1925 NM_017346 Huesken Cacnb1 782 CAGCCCUCCAGCUCAUUCUua AGAAUGAGCUGGAGGGCUG -2.1 -2.1 -2.9 2 -2 4 -42.7 64.8 -8.3 2 III 57.9 48.7 75.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1926 NM_017346 Huesken Cacnb1 782 AGCCCUCCAGCUCAUUCUUau AAGAAUGAGCUGGAGGGCU -0.9 -2.1 -2.2 2 0 4 -41.5 56.8 -0.9 1 II 52.6 40.1 54.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1927 NM_017346 Huesken Cacnb1 782 UUGCGCCCCAGAACCGGCCca GGCCGGUUCUGGGGCGCAA -3.3 -0.9 -4.4 2 4 7 -47.5 45.1 4.8 3 II 73.7 67.7 79.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1928 NM_017346 Huesken Cacnb1 782 GGCCCACCACCCUCCGCACag GUGCGGAGGGUGGUGGGCC -2.2 -3.3 -0.5 1 0 5 -49.7 29.1 2.7 -1 II 78.9 25.2 52.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1929 NM_017346 Huesken Cacnb1 782 CCUCCUCUUCCCAGGAGCCcu GGCUCCUGGGAAGAGGAGG -3.3 -3.3 -6.7 -1 1 3 -46.3 39.1 -1.9 -1 II 68.4 41.2 46.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1930 NM_017346 Huesken Cacnb1 782 GAGUCUCCUGGCUCCGUGUag ACACGGAGCCAGGAGACUC -2.2 -2.4 -1.8 0 -1 3 -44.5 56.8 -6.3 1 III 63.2 38.4 48.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1931 NM_017346 Huesken Cacnb1 782 AGUCUCCUGGCUCCGUGUAga UACACGGAGCCAGGAGACU -1.3 -2.1 -1.7 3 0 3 -43.4 52.7 -0.7 2 II 57.9 35.6 54.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1932 NM_017346 Huesken Cacnb1 782 CCGUGUAGACAGAGUUUCGgc CGAAACUCUGUCUACACGG -2.4 -3.3 -0.3 -2 -1 3 -37.7 52.6 -2.3 3 II 52.6 44.5 44 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1933 NM_017346 Huesken Cacnb1 782 UCAAAGGUGUCUUGGCGGGau CCCGCCAAGACACCUUUGA -3.3 -2.4 0.1 0 4 6 -41.4 51.7 3.4 6 Ib 57.9 58.4 57.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1934 NM_017346 Huesken Cacnb1 782 AGGUGUCUUGGCGGGAUAGcg CUAUCCCGCCAAGACACCU -2.1 -2.1 2.2 0 1 6 -42 49.4 -2.4 3 II 57.9 43.2 70.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1935 NM_017346 Huesken Cacnb1 782 GGCCAGGUGGGUGGUUGCUgg AGCAACCACCCACCUGGCC -2.1 -3.3 -1.1 1 -1 4 -46.7 26.9 1.8 0 III 68.4 24.5 31.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1936 NM_017346 Huesken Cacnb1 782 GGGGCUGGCCCAGCUCCCCgg GGGGAGCUGGGCCAGCCCC -3.3 -3.3 -4.6 1 1 5 -52.8 21.5 5.1 -1 II 84.2 39.2 19.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1937 NM_017346 Huesken Cacnb1 782 GGUAGCCAUGGUGCGGUUCag GAACCGCACCAUGGCUACC -2.4 -3.3 -0.9 0 0 4 -43.1 47.5 10.4 2 II 63.2 36.4 49 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1938 NM_017346 Huesken Cacnb1 782 UCAGCAGCGGAUUGGGUGGcg CCACCCAAUCCGCUGCUGA -3.3 -2.4 2.1 0 3 4 -44 51 5.3 5 II 63.2 56.9 81.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1939 NM_017346 Huesken Cacnb1 782 CUUCCAGUAGGCUUCCAAGua CUUGGAAGCCUACUGGAAG -2.1 -2.1 -1 0 1 3 -39 63.2 -2 2 II 52.6 47 60.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1940 NM_017346 Huesken Cacnb1 782 AGGCAUCUUCCAAUUGGUUcu AACCAAUUGGAAGAUGCCU -0.9 -2.1 -1.1 2 1 3 -36.6 57.8 -3.9 2 II 42.1 44.9 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1941 NM_017346 Huesken Cacnb1 782 CAAUUGGUUCUCGUCCAGGau CCUGGACGAGAACCAAUUG -3.3 -2.1 -1 -1 2 2 -38.2 57.8 -2 4 II 52.6 57.1 80.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1942 NM_017346 Huesken Cacnb1 782 UGAUGAGCCUCUGCAGUACcu GUACUGCAGAGGCUCAUCA -2.2 -2.1 -0.4 1 2 3 -40.9 58.1 8.1 7 Ib 52.6 55.5 73.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1943 NM_017346 Huesken Cacnb1 782 AGCGAGGUUUUAGAGAGCUgg AGCUCUCUAAAACCUCGCU -2.1 -2.1 0.4 1 1 3 -38.5 43.5 -1.3 4 II 47.4 49.4 56.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1944 NM_017346 Huesken Cacnb1 782 GAUCCGCUCGAUUUCACUCug GAGUGAAAUCGAGCGGAUC -2.4 -2.4 0.2 2 3 4 -38.4 70.4 15.1 2 II 52.6 50.8 84.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1945 NM_017346 Huesken Cacnb1 782 AUUUCACUCUGUACCUCAGcc CUGAGGUACAGAGUGAAAU -2.1 -1.1 -0.8 2 4 2 -36 78.7 0.4 5 Ia 42.1 55.1 59.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1946 NM_017346 Huesken Cacnb1 782 CACUCUGUACCUCAGCCAGgc CUGGCUGAGGUACAGAGUG -2.1 -2.1 -1.3 -1 0 3 -41.6 60.1 1.1 1 II 57.9 44 34.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1947 NM_017346 Huesken Cacnb1 782 GCGAGUGUUGGAGCGCUCGau CGAGCGCUCCAACACUCGC -2.4 -3.4 -1.9 0 0 4 -43.7 37.9 0 1 II 68.4 43.5 15.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1948 NM_017346 Huesken Cacnb1 782 AUAAUGUGUUUGCUGGGGUug ACCCCAGCAAACACAUUAU -2.2 -1.1 3.9 2 4 4 -36.6 70.3 0.8 7 II 42.1 61.1 63.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1949 NM_017346 Huesken Cacnb1 782 UUGAGCGAUGGUCCCACCAgg UGGUGGGACCAUCGCUCAA -2.1 -0.9 -4 0 1 3 -43.1 58.4 1.7 4 II 57.9 61.8 71.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1950 NM_017346 Huesken Cacnb1 782 GGGGCACGUGCUCUGUCGAcu UCGACAGAGCACGUGCCCC -2.4 -3.3 -0.6 0 -1 5 -45.8 33.9 1.7 -1 III 68.4 22 39.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1951 NM_017346 Huesken Cacnb1 782 UUCUGCUUCUGUUUGGCACug GUGCCAAACAGAAGCAGAA -2.2 -0.9 -0.6 2 4 3 -37.6 89.7 12.8 6 Ib 47.4 66.9 82.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1952 NM_017346 Huesken Cacnb1 782 UGCUGGAGCUGAGGCGGUUuu AACCGCCUCAGCUCCAGCA -0.9 -2.1 -1.4 0 0 5 -45.1 35.7 -4 3 II 63.2 42.7 46.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1953 NM_017346 Huesken Cacnb1 782 GAGCUGAGGCGGUUUUGGCgc GCCAAAACCGCCUCAGCUC -3.4 -2.4 -0.3 2 3 5 -42.7 51.1 9.7 2 II 63.2 45.7 54.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1954 NM_017346 Huesken Cacnb1 782 AGCAGGCGAAGGCUGUCCAgu UGGACAGCCUUCGCCUGCU -2.1 -2.1 -0.5 1 1 4 -45.1 45.6 1 3 II 63.2 40.1 39.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1955 NM_017346 Huesken Cacnb1 782 GACAGGGCUGGGGAUGAAAcc UUUCAUCCCCAGCCCUGUC -0.9 -2.4 1.4 0 -3 4 -42.7 35.1 -3.8 2 III 57.9 27.2 16.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1956 NM_017346 Huesken Cacnb1 782 UCCUUCACCAGCCUCCCGAuc UCGGGAGGCUGGUGAAGGA -2.4 -2.4 -0.9 1 1 4 -45.5 61.6 -1.4 6 II 63.2 54.6 73.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1957 NM_017346 Huesken Cacnb1 782 CAGCCUCCCGAUCCACCAGuc CUGGUGGAUCGGGAGGCUG -2.1 -2.1 -1 1 0 4 -45.4 46.7 5.7 -1 II 68.4 40.7 40.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1958 NM_017346 Huesken Cacnb1 782 UUCUCCUUGAUGUGCAGGAag UCCUGCACAUCAAGGAGAA -2.4 -0.9 -3.9 1 1 2 -39.4 73.7 -3.8 6 II 47.4 59.7 94 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1959 NM_017346 Huesken Cacnb1 782 AUGUGCAGGAAGUCCUUGGgc CCAAGGACUUCCUGCACAU -3.3 -1.1 -2.4 2 3 2 -40.1 70.1 2.3 6 Ib 52.6 64.7 63.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1960 NM_017346 Huesken Cacnb1 782 ACUGGCACCUCAUCUCCUGga CAGGAGAUGAGGUGCCAGU -2.1 -2.2 0 2 3 3 -42.8 51 -2.4 3 II 57.9 52.6 83.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1961 NM_017346 Huesken Cacnb1 782 ACGGAUUGUAGCCAACAUUug AAUGUUGGCUACAAUCCGU -0.9 -2.2 -1 2 -1 3 -36 59.5 -1.2 4 II 42.1 52.6 90.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1962 NM_017346 Huesken Cacnb1 782 CUUUCUCGAGCUGGGCUAAgg UUAGCCCAGCUCGAGAAAG -0.9 -2.1 0.4 -2 -3 4 -39.6 53.1 -5.1 4 II 52.6 28.6 63.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1963 NM_017346 Huesken Cacnb1 782 UUCUCGAGCUGGGCUAAGGcc CCUUAGCCCAGCUCGAGAA -3.3 -0.9 0.4 1 3 4 -42 62.5 0 5 Ib 57.9 64.1 76.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1964 NM_017346 Huesken Cacnb1 782 GACACGUCGGAGUCUGACGgc CGUCAGACUCCGACGUGUC -2.4 -2.4 -3.2 2 1 3 -41.9 57.9 2.3 1 II 63.2 49.6 77 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1965 NM_017346 Huesken Cacnb1 782 CGGAGUCUGACGGCCGGCUcg AGCCGGCCGUCAGACUCCG -2.1 -2.4 0 0 -2 8 -47.2 30.7 -8.3 1 III 73.7 35.2 44.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1966 NM_017346 Huesken Cacnb1 782 GGCUCGUGUAGGACUCUGCug GCAGAGUCCUACACGAGCC -3.4 -3.3 1.2 1 0 3 -43.5 54.7 4.8 3 II 63.2 44.3 79.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1967 NM_017346 Huesken Cacnb1 782 GACCUUUUGAACCGCCCUUuc AAGGGCGGUUCAAAAGGUC -0.9 -2.4 0 2 -1 6 -39 58.2 -1.6 4 II 52.6 42.2 57.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1968 NM_017346 Huesken Cacnb1 782 CUGUAUUUGCCCUGUGGGCug GCCCACAGGGCAAAUACAG -3.4 -2.1 -6 0 1 4 -41.2 58.8 3.4 2 II 57.9 50.7 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1969 NM_017346 Huesken Cacnb1 782 AGACCUCCAUAGGGAUCUCuu GAGAUCCCUAUGGAGGUCU -2.4 -2.1 -2.7 1 3 3 -41.4 48.8 9.7 2 II 52.6 45.3 71.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1970 NM_012864 Huesken Mmp7 4316 UGUCGUCCUUUGUAAGACUga AGUCUUACAAAGGACGACA -2.1 -2.1 -4.1 1 1 2 -36.2 64.7 -4 3 II 42.1 57.1 98.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1971 NM_012864 Huesken Mmp7 4316 UCCUUUGUAAGACUGAAGUcu ACUUCAGUCUUACAAAGGA -2.2 -2.4 0.3 0 1 2 -34.6 85 0.8 7 II 36.8 62 111.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1972 NM_012864 Huesken Mmp7 4316 CCUUUGUAAGACUGAAGUCuu GACUUCAGUCUUACAAAGG -2.4 -3.3 -1.9 -1 0 2 -34.6 66.1 5.4 3 II 42.1 47.4 92.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1973 NM_012864 Huesken Mmp7 4316 AAGACUGAAGUCUUCUGAAug UUCAGAAGACUUCAGUCUU -0.9 -0.9 -3.6 1 1 1 -34.7 73.8 -3.8 4 II 36.8 51.2 92.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1974 NM_012864 Huesken Mmp7 4316 ACUGAAGUCUUCUGAAUGAuc UCAUUCAGAAGACUUCAGU -2.4 -2.2 1 1 0 1 -34.9 57.4 -3.4 6 II 36.8 43.6 54.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1975 NM_012864 Huesken Mmp7 4316 UGAAUGAUCUCCUUGAUAGgu CUAUCAAGGAGAUCAUUCA -2.1 -2.1 -0.2 1 3 2 -34.3 87.2 -2.4 8 Ia 36.8 69.5 115.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1976 NM_012864 Huesken Mmp7 4316 UGAUCUCCUUGAUAGGUAGgg CUACCUAUCAAGGAGAUCA -2.1 -2.1 -1.9 0 2 2 -36.7 77.8 0 5 Ib 42.1 58.9 114.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1977 NM_012864 Huesken Mmp7 4316 AUCUCCUUGAUAGGUAGGGua CCCUACCUAUCAAGGAGAU -3.3 -1.1 -1.9 2 4 3 -38.8 66.3 0 5 Ib 47.4 60.8 102.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1978 NM_012864 Huesken Mmp7 4316 AUAGGUAGGGUACAUCACAga UGUGAUGUACCCUACCUAU -2.1 -1.1 1.1 2 1 3 -37.7 53.7 -1.4 5 II 42.1 60.6 107.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1979 NM_012864 Huesken Mmp7 4316 AGGUAGGGUACAUCACAGAac UCUGUGAUGUACCCUACCU -2.4 -2.1 1.1 1 -1 3 -39.8 50.9 -3.4 6 II 47.4 46.1 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1980 NM_012864 Huesken Mmp7 4316 GUAGGGUACAUCACAGAACug GUUCUGUGAUGUACCCUAC -2.2 -2.2 1.9 2 1 3 -37.5 53.2 2.5 4 II 47.4 55.1 104.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1981 NM_012864 Huesken Mmp7 4316 UAGGGUACAUCACAGAACUgg AGUUCUGUGAUGUACCCUA -2.1 -1.3 2.2 0 1 3 -37.4 65.1 -3.9 5 II 42.1 67.1 116.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1982 NM_012864 Huesken Mmp7 4316 UCACAGAACUGGGAACAGAag UCUGUUCCCAGUUCUGUGA -2.4 -2.4 -0.3 2 0 3 -39.3 44 -1.1 6 II 47.4 51.2 99.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1983 NM_012864 Huesken Mmp7 4316 GAACUGGGAACAGAAGAGUga ACUCUUCUGUUCCCAGUUC -2.2 -2.4 -0.3 1 0 3 -38.1 42.2 -6.3 5 III 47.4 43.4 81.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1984 NM_012864 Huesken Mmp7 4316 CAGAAGAGUGACCCAGACCca GGUCUGGGUCACUCUUCUG -3.3 -2.1 -1.4 -1 0 3 -41.7 50.3 10.5 2 II 57.9 56.5 73.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1985 NM_012864 Huesken Mmp7 4316 AAGAGUGACCCAGACCCAGag CUGGGUCUGGGUCACUCUU -2.1 -0.9 -1.2 2 3 3 -42.6 43.6 -2.4 3 Ib 57.9 57.1 87.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1986 NM_012864 Huesken Mmp7 4316 GUGACCCAGACCCAGAGAGug CUCUCUGGGUCUGGGUCAC -2.1 -2.2 -0.4 1 1 3 -44.1 46.1 -2.3 2 II 63.2 40.5 73.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1987 NM_012864 Huesken Mmp7 4316 UGACCCAGACCCAGAGAGUgg ACUCUCUGGGUCUGGGUCA -2.2 -2.1 -1 0 1 3 -44.1 42.7 -11.3 3 II 57.9 49.6 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1988 NM_012864 Huesken Mmp7 4316 CCCAGACCCAGAGAGUGGCca GCCACUCUCUGGGUCUGGG -3.4 -3.3 -1.5 0 0 3 -46.2 32.8 5.4 0 II 68.4 37.7 63.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1989 NM_012864 Huesken Mmp7 4316 CCAGACCCAGAGAGUGGCCaa GGCCACUCUCUGGGUCUGG -3.3 -3.3 -4.3 -2 1 4 -46.2 30.1 7.8 0 II 68.4 39.4 41.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1990 NM_012864 Huesken Mmp7 4316 GGCCAAGUUCAUGAGUGGCaa GCCACUCAUGAACUUGGCC -3.4 -3.3 -3.3 1 1 4 -41.4 43.5 15.4 0 II 57.9 36.8 62.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1991 NM_012864 Huesken Mmp7 4316 UCAUGAGUGGCAACAAACAgg UGUUUGUUGCCACUCAUGA -2.1 -2.4 1.5 1 0 3 -36.6 53.8 -8.7 6 II 42.1 56.4 104.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1992 NM_012864 Huesken Mmp7 4316 GAGUGGCAACAAACAGGAAgu UUCCUGUUUGUUGCCACUC -0.9 -2.4 1.5 0 -2 3 -37.6 41.6 -4 2 III 47.4 25.9 37.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1993 NM_012864 Huesken Mmp7 4316 GGCAACAAACAGGAAGUUCac GAACUUCCUGUUUGUUGCC -2.4 -3.3 -1 0 -1 3 -36.4 52.7 12.4 3 II 47.4 40.7 53.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1994 NM_012864 Huesken Mmp7 4316 GCAACAAACAGGAAGUUCAcg UGAACUUCCUGUUUGUUGC -2.1 -3.4 -1.2 1 -2 2 -35.2 59 -6.3 4 II 42.1 42.2 33.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1995 NM_012864 Huesken Mmp7 4316 AAACAGGAAGUUCACGCCUga AGGCGUGAACUUCCUGUUU -2.1 -0.9 -0.5 2 3 4 -37.9 52.6 4.2 6 II 47.4 61 91.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1996 NM_012864 Huesken Mmp7 4316 AGGAAGUUCACGCCUGAGUcc ACUCAGGCGUGAACUUCCU -2.2 -2.1 0.5 3 0 4 -40.6 60.2 -1.2 6 II 52.6 52.6 73.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1997 NM_012864 Huesken Mmp7 4316 GAAGUUCACGCCUGAGUCCuc GGACUCAGGCGUGAACUUC -3.3 -2.4 0.5 0 2 4 -40.9 51.6 2.7 3 II 57.9 50.4 70.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1998 NM_012864 Huesken Mmp7 4316 UUCACGCCUGAGUCCUCACca GUGAGGACUCAGGCGUGAA -2.2 -0.9 -0.6 0 3 4 -42.1 67.3 9.7 4 II 57.9 62.6 89.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si1999 NM_012864 Huesken Mmp7 4316 UCACGCCUGAGUCCUCACCau GGUGAGGACUCAGGCGUGA -3.3 -2.4 -0.6 2 3 4 -44.5 57.9 12.8 4 II 63.2 62.5 94.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2000 NM_012864 Huesken Mmp7 4316 CACGCCUGAGUCCUCACCAuc UGGUGAGGACUCAGGCGUG -2.1 -2.1 -0.6 0 -1 4 -44.2 48.6 -3.4 1 III 63.2 43.5 69.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2001 NM_012864 Huesken Mmp7 4316 ACGCCUGAGUCCUCACCAUcc AUGGUGAGGACUCAGGCGU -1.1 -2.2 -0.6 3 0 4 -43.2 43.1 -8.7 2 II 57.9 38.1 65.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2002 NM_012864 Huesken Mmp7 4316 CGCCUGAGUCCUCACCAUCcg GAUGGUGAGGACUCAGGCG -2.4 -2.4 -0.6 0 -2 4 -43.4 42.7 8.5 1 II 63.2 43.3 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2003 NM_012864 Huesken Mmp7 4316 GAGUCCUCACCAUCCGUCCag GGACGGAUGGUGAGGACUC -3.3 -2.4 0.8 1 1 3 -43.7 62.2 5.1 3 II 63.2 51.8 81.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2004 NM_012864 Huesken Mmp7 4316 AGUCCUCACCAUCCGUCCAgu UGGACGGAUGGUGAGGACU -2.1 -2.1 0.9 3 1 3 -43.4 58.5 4 2 II 57.9 42.9 52.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2005 NM_012864 Huesken Mmp7 4316 UCCUCACCAUCCGUCCAGUac ACUGGACGGAUGGUGAGGA -2.2 -2.4 0.3 0 1 3 -43.4 52.6 -6.3 3 II 57.9 44.4 46.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2006 NM_012864 Huesken Mmp7 4316 CCUCACCAUCCGUCCAGUAcu UACUGGACGGAUGGUGAGG -1.3 -3.3 -0.8 0 -3 3 -42.3 39.7 -5.4 1 III 57.9 26.6 32.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2007 NM_012864 Huesken Mmp7 4316 UCACCAUCCGUCCAGUACUca AGUACUGGACGGAUGGUGA -2.1 -2.4 -1 3 1 3 -41.2 58.6 -3.9 4 II 52.6 61.3 90.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2008 NM_012864 Huesken Mmp7 4316 ACCAUCCGUCCAGUACUCAuc UGAGUACUGGACGGAUGGU -2.1 -2.2 0.7 1 0 3 -41.2 49.4 -3.8 5 II 52.6 40.6 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2009 NM_012864 Huesken Mmp7 4316 CCAUCCGUCCAGUACUCAUcc AUGAGUACUGGACGGAUGG -1.1 -3.3 0.7 0 -2 3 -40.1 58.2 -3.7 3 III 52.6 35.8 41.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2010 NM_012864 Huesken Mmp7 4316 CAUCCGUCCAGUACUCAUCcu GAUGAGUACUGGACGGAUG -2.4 -2.1 0.7 2 0 3 -39.2 68.7 5.8 4 II 52.6 56.8 87.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2011 NM_012864 Huesken Mmp7 4316 CCGUCCAGUACUCAUCCUUgu AAGGAUGAGUACUGGACGG -0.9 -3.3 0.6 -1 -3 3 -39.9 56.1 -2.9 3 III 52.6 38.8 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2012 NM_012864 Huesken Mmp7 4316 CAUCCUUGUCAAAGUGAGCau GCUCACUUUGACAAGGAUG -3.4 -2.1 0.7 0 1 2 -36.8 62.2 5.1 3 II 47.4 52.8 101.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2013 NM_012864 Huesken Mmp7 4316 UCAAAGUGAGCAUCUCCGCcg GCGGAGAUGCUCACUUUGA -3.4 -2.4 -1.8 1 4 4 -39.8 60.7 7.8 6 Ia 52.6 69.3 108.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2014 NM_012864 Huesken Mmp7 4316 AAAGUGAGCAUCUCCGCCGag CGGCGGAGAUGCUCACUUU -2.4 -0.9 -2.1 2 5 6 -41 58.7 -2.4 5 Ia 57.9 74 118.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2015 NM_012864 Huesken Mmp7 4316 GUGAGCAUCUCCGCCGAGGcc CCUCGGCGGAGAUGCUCAC -3.3 -2.2 -2.1 1 1 6 -44.9 41.5 -4.7 1 II 68.4 46.3 72.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2016 NM_012864 Huesken Mmp7 4316 UGAGCAUCUCCGCCGAGGCcu GCCUCGGCGGAGAUGCUCA -3.4 -2.1 -2.4 1 4 6 -46.1 49.8 7.5 3 Ib 68.4 61.7 90.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2017 NM_012864 Huesken Mmp7 4316 AGCAUCUCCGCCGAGGCCUgg AGGCCUCGGCGGAGAUGCU -2.1 -2.1 -2.4 3 1 6 -47 45.2 -8.7 3 II 68.4 50.3 68.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2018 NM_012864 Huesken Mmp7 4316 AUCUCCGCCGAGGCCUGGCcc GCCAGGCCUCGGCGGAGAU -3.4 -1.1 -4 2 4 6 -48.2 48.9 9.7 3 II 73.7 55.3 36.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2019 NM_012864 Huesken Mmp7 4316 UCCGCCGAGGCCUGGCCCCgg GGGGCCAGGCCUCGGCGGA -3.3 -2.4 -6.3 0 3 6 -52.5 29.8 2.7 2 II 84.2 53.9 50.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2020 NM_012864 Huesken Mmp7 4316 GCCGAGGCCUGGCCCCGGUgc ACCGGGGCCAGGCCUCGGC -2.2 -3.4 -11.2 1 -1 8 -52.3 15.1 1.1 0 III 84.2 23.7 11 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2021 NM_012864 Huesken Mmp7 4316 CUGGCCCCGGUGCAAAGGCau GCCUUUGCACCGGGGCCAG -3.4 -2.1 -4.8 0 1 8 -46.9 31.8 7.8 -1 II 73.7 44.9 32.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2022 NM_012864 Huesken Mmp7 4316 UGGCCCCGGUGCAAAGGCAug UGCCUUUGCACCGGGGCCA -2.1 -2.1 -4.8 2 0 8 -46.9 33.2 -8.7 1 II 68.4 41 59.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2023 NM_012864 Huesken Mmp7 4316 AAAGGCAUGGCCUAGAGUGuu CACUCUAGGCCAUGCCUUU -2.1 -0.9 -2.9 2 4 4 -40.2 56 -4.7 4 Ib 52.6 63.3 100.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2024 NM_012864 Huesken Mmp7 4316 GCAUGGCCUAGAGUGUUUCcu GAAACACUCUAGGCCAUGC -2.4 -3.4 1.5 0 1 4 -39.4 53.3 9.7 4 II 52.6 42.2 53.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2025 NM_012864 Huesken Mmp7 4316 CAUGGCCUAGAGUGUUUCCug GGAAACACUCUAGGCCAUG -3.3 -2.1 0.4 -2 1 4 -39.3 62.2 7.7 3 II 52.6 48.2 89.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2026 NM_012864 Huesken Mmp7 4316 GGCCUAGAGUGUUUCCUGGcc CCAGGAAACACUCUAGGCC -3.3 -3.3 0.1 2 1 4 -41.5 54.4 5.4 2 II 57.9 37.8 33.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2027 NM_012864 Huesken Mmp7 4316 CCUAGAGUGUUUCCUGGCCca GGCCAGGAAACACUCUAGG -3.3 -3.3 0.1 0 1 4 -41.5 50.5 10.8 2 II 57.9 45 54.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2028 NM_012864 Huesken Mmp7 4316 CUAGAGUGUUUCCUGGCCCau GGGCCAGGAAACACUCUAG -3.3 -2.1 0.1 0 3 5 -41.5 52.5 10.5 3 II 57.9 60.4 83.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2029 NM_012864 Huesken Mmp7 4316 GUUUCCUGGCCCAUCAAAUgg AUUUGAUGGGCCAGGAAAC -1.1 -2.2 0.1 2 0 5 -37.8 66.6 -8.9 4 II 47.4 41.5 10.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2030 NM_012864 Huesken Mmp7 4316 UGGCCCAUCAAAUGGGAAGuu CUUCCCAUUUGAUGGGCCA -2.1 -2.1 -4.1 1 1 5 -40.1 64.6 2.3 4 II 52.6 57.3 85 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2031 NM_012864 Huesken Mmp7 4316 GCCCAUCAAAUGGGAAGUUgu AACUUCCCAUUUGAUGGGC -0.9 -3.4 -4.1 0 -2 4 -37.8 36.4 -1.3 1 III 47.4 25.8 0.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2032 NM_012864 Huesken Mmp7 4316 GUUGUCUCCGUGAUCUCCCcu GGGAGAUCACGGAGACAAC -3.3 -2.2 0.8 2 4 3 -41.3 63.5 7.1 3 II 57.9 61.5 94.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2033 NM_012864 Huesken Mmp7 4316 UGUCUCCGUGAUCUCCCCUug AGGGGAGAUCACGGAGACA -2.1 -2.1 -0.7 1 3 4 -43.6 64.4 6.1 4 II 57.9 57.1 101.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2034 NM_012864 Huesken Mmp7 4316 CUCCGUGAUCUCCCCUUGCga GCAAGGGGAGAUCACGGAG -3.4 -2.1 -0.7 0 0 4 -43.3 47.7 5.5 2 II 63.2 51.1 90.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2035 NM_012864 Huesken Mmp7 4316 UCCGUGAUCUCCCCUUGCGaa CGCAAGGGGAGAUCACGGA -2.4 -2.4 -0.7 1 3 4 -43.6 55.4 -2.3 4 II 63.2 60.9 97.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2036 NM_012864 Huesken Mmp7 4316 CGUGAUCUCCCCUUGCGAAgc UUCGCAAGGGGAGAUCACG -0.9 -2.4 -1.9 0 -2 4 -41.2 49.4 -5.4 0 III 57.9 28 26.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2037 NM_012864 Huesken Mmp7 4316 UGAUCUCCCCUUGCGAAGCca GCUUCGCAAGGGGAGAUCA -3.4 -2.1 -5 1 3 4 -42.1 65.5 10.4 3 Ib 57.9 64.4 105.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2038 NM_012864 Huesken Mmp7 4316 CCUUGCGAAGCCAAUUAUGau CAUAAUUGGCUUCGCAAGG -2.1 -3.3 -1 -1 -1 3 -35.8 53.4 -9.3 2 II 47.4 43.4 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2039 NM_012864 Huesken Mmp7 4316 CUUGCGAAGCCAAUUAUGAug UCAUAAUUGGCUUCGCAAG -2.4 -2.1 0.4 0 -1 3 -34.9 59.1 -8.4 4 III 42.1 46.2 75.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2040 NM_012864 Huesken Mmp7 4316 GAAGCCAAUUAUGAUGUCUgc AGACAUCAUAAUUGGCUUC -2.1 -2.4 0.6 0 0 3 -33.9 68.6 1.4 4 III 36.8 47.9 99.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2041 NM_012864 Huesken Mmp7 4316 AAGCCAAUUAUGAUGUCUGca CAGACAUCAUAAUUGGCUU -2.1 -0.9 0.6 2 4 3 -33.6 74.7 -0.3 5 Ib 36.8 66.6 102.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2042 NM_012864 Huesken Mmp7 4316 AGCCAAUUAUGAUGUCUGCag GCAGACAUCAUAAUUGGCU -3.4 -2.1 0.6 2 2 3 -36.1 65.6 10.1 5 Ib 42.1 50.9 95.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2043 NM_012864 Huesken Mmp7 4316 CCCCAACUAACCCUCUUGAag UCAAGAGGGUUAGUUGGGG -2.4 -3.3 1.4 0 -3 4 -40.2 49.7 -3 3 III 52.6 29.4 40.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2044 NM_012864 Huesken Mmp7 4316 AGUGGGAUUUGCAUACUCCac GGAGUAUGCAAAUCCCACU -3.3 -2.1 -1.2 1 4 3 -38.3 63.7 4.8 4 II 47.4 63.2 96.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2045 NM_012864 Huesken Mmp7 4316 CUGGAAUGCCACUUAGGACug GUCCUAAGUGGCAUUCCAG -2.2 -2.1 -1.1 1 1 3 -39.3 57.7 10.4 2 II 52.6 48.3 109.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2046 NM_012864 Huesken Mmp7 4316 GAAUGCCACUUAGGACUGUuu ACAGUCCUAAGUGGCAUUC -2.2 -2.4 -1.3 0 0 3 -38.2 43.1 -4 3 III 47.4 34.4 65.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2047 NM_012864 Huesken Mmp7 4316 UGCCACUUAGGACUGUUUGgc CAAACAGUCCUAAGUGGCA -2.1 -2.1 -1.3 2 2 3 -37.7 74.6 7.4 5 II 47.4 60.7 81.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2048 NM_012864 Huesken Mmp7 4316 UUAGGACUGUUUGGCAUUAgu UAAUGCCAAACAGUCCUAA -1.3 -0.9 1.8 0 0 3 -34.6 58.9 -0.7 6 II 36.8 52.8 105 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2049 NM_012864 Huesken Mmp7 4316 UGGCAUUAGUGAGAAUUCUgc AGAAUUCUCACUAAUGCCA -2.1 -2.1 0.8 3 0 3 -34.9 65.6 -1.3 6 II 36.8 59.4 106.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2050 NM_012864 Huesken Mmp7 4316 GCAUUAGUGAGAAUUCUGCaa GCAGAAUUCUCACUAAUGC -3.4 -3.4 0.2 1 2 2 -35 68 7.1 6 II 42.1 51.4 94.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2051 NM_012864 Huesken Mmp7 4316 CAUUAGUGAGAAUUCUGCAac UGCAGAAUUCUCACUAAUG -2.1 -2.1 0.8 0 0 2 -33.7 75.1 1.6 5 II 36.8 49.7 72.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2052 NM_012864 Huesken Mmp7 4316 UUAGUGAGAAUUCUGCAACau GUUGCAGAAUUCUCACUAA -2.2 -0.9 0.8 0 4 2 -33.6 82.9 15.2 8 Ia 36.8 77.6 122.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2053 NM_012864 Huesken Mmp7 4316 AGUGAGAAUUCUGCAACAUcu AUGUUGCAGAAUUCUCACU -1.1 -2.1 0.8 1 1 2 -34.6 57.2 -0.6 5 II 36.8 45.9 80.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2054 NM_012864 Huesken Mmp7 4316 GUGAGAAUUCUGCAACAUCug GAUGUUGCAGAAUUCUCAC -2.4 -2.2 0.8 0 0 2 -34.9 57.4 9.8 3 II 42.1 52.1 119.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2055 NM_012864 Huesken Mmp7 4316 GAAUUCUGCAACAUCUGGCac GCCAGAUGUUGCAGAAUUC -3.4 -2.4 -0.3 2 4 3 -37 77 7.1 6 II 47.4 61.1 100.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2056 NM_012864 Huesken Mmp7 4316 UUCUGCAACAUCUGGCACUcc AGUGCCAGAUGUUGCAGAA -2.1 -0.9 -1.2 0 1 3 -39 69.4 -6.3 6 II 47.4 66.4 115 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2057 NM_012864 Huesken Mmp7 4316 UCUGCAACAUCUGGCACUCca GAGUGCCAGAUGUUGCAGA -2.4 -2.4 -1.2 -1 3 3 -40.5 54.9 8.1 4 Ib 52.6 57.3 104 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2058 NM_012864 Huesken Mmp7 4316 UGCAACAUCUGGCACUCCAca UGGAGUGCCAGAUGUUGCA -2.1 -2.1 -1.4 1 0 3 -41.4 61.8 1.4 5 II 52.6 54.3 91.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2059 NM_012864 Huesken Mmp7 4316 AACAUCUGGCACUCCACACcu GUGUGGAGUGCCAGAUGUU -2.2 -0.9 -1.6 3 3 3 -40.3 71.6 7.4 5 Ia 52.6 61.1 93.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2060 NM_012864 Huesken Mmp7 4316 UCUGGCACUCCACACCUGGgc CCAGGUGUGGAGUGCCAGA -3.3 -2.4 -2.2 0 3 3 -44.8 48.4 0.1 4 II 63.2 62.8 85.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2061 NM_012864 Huesken Mmp7 4316 CUGGCACUCCACACCUGGGcu CCCAGGUGUGGAGUGCCAG -3.3 -2.1 -2.2 0 1 3 -45.7 42.3 -4.6 -1 II 68.4 44.8 60.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2062 NM_012864 Huesken Mmp7 4316 GCACUCCACACCUGGGCUUcu AAGCCCAGGUGUGGAGUGC -0.9 -3.4 -1.4 1 -1 4 -44.6 37.2 -8.7 1 III 63.2 29 47.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2063 NM_012864 Huesken Mmp7 4316 CACUCCACACCUGGGCUUCug GAAGCCCAGGUGUGGAGUG -2.4 -2.1 -1.4 -2 -1 4 -43.6 51.8 6.1 2 II 63.2 41.9 94 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2064 NM_012864 Huesken Mmp7 4316 CCACACCUGGGCUUCUGCAuu UGCAGAAGCCCAGGUGUGG -2.1 -3.3 -0.3 1 -1 4 -44.5 42.3 -3.1 1 III 63.2 32.5 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2065 NM_012864 Huesken Mmp7 4316 ACACCUGGGCUUCUGCAUUau AAUGCAGAAGCCCAGGUGU -0.9 -2.2 -0.3 3 1 4 -41.1 54.4 3.8 4 II 52.6 47.2 86.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2066 NM_012864 Huesken Mmp7 4316 CUUCUGCAUUAUCUCCAUGac CAUGGAGAUAAUGCAGAAG -2.1 -2.1 0.9 0 1 2 -35 71.3 8.1 3 II 42.1 50.9 97.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2067 NM_012864 Huesken Mmp7 4316 UCUGCAUUAUCUCCAUGACac GUCAUGGAGAUAAUGCAGA -2.2 -2.4 0.1 1 3 2 -36.6 75.7 10.5 5 Ib 42.1 56.5 115 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2068 NM_012864 Huesken Mmp7 4316 UGCAUUAUCUCCAUGACACgg GUGUCAUGGAGAUAAUGCA -2.2 -2.1 -1.2 1 3 2 -36.4 81.5 2.4 5 Ia 42.1 68 112.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2069 NM_012864 Huesken Mmp7 4316 GGACAGCUUUCCAGUCUCCgg GGAGACUGGAAAGCUGUCC -3.3 -3.3 -1.2 0 1 2 -41.7 39.3 2.8 1 II 57.9 40.4 88.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2070 NM_012864 Huesken Mmp7 4316 GCUUUCCAGUCUCCGGCAAac UUGCCGGAGACUGGAAAGC -0.9 -3.4 -2.4 1 -2 5 -41.7 47.4 -0.7 1 III 57.9 18.8 1.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2071 NM_012864 Huesken Mmp7 4316 UUCCAGUCUCCGGCAAACCga GGUUUGCCGGAGACUGGAA -3.3 -0.9 -2.4 2 3 5 -41.7 55.5 7.8 4 Ib 57.9 70.4 102.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2072 NM_012864 Huesken Mmp7 4316 UCCGGCAAACCGAAGAACUuc AGUUCUUCGGUUUGCCGGA -2.1 -2.4 -4.7 0 0 5 -39.6 48.7 -8.9 3 II 52.6 56.1 53.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2073 NM_012864 Huesken Mmp7 4316 CCGGCAAACCGAAGAACUUcu AAGUUCUUCGGUUUGCCGG -0.9 -3.3 -3.7 -1 -3 5 -38.1 33.2 -8.6 0 III 52.6 32 1.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2074 NM_012864 Huesken Mmp7 4316 GAACUUCUGCAUUUCCCUCag GAGGGAAAUGCAGAAGUUC -2.4 -2.4 1.8 2 3 3 -37 73.4 15.1 3 II 47.4 53.1 97.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2075 NM_012864 Huesken Mmp7 4316 AACUUCUGCAUUUCCCUCAgu UGAGGGAAAUGCAGAAGUU -2.1 -0.9 1.8 3 0 3 -36.7 85.2 -0.7 8 II 42.1 62 103.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2076 NM_012864 Huesken Mmp7 4316 ACUUCUGCAUUUCCCUCAGuu CUGAGGGAAAUGCAGAAGU -2.1 -2.2 -0.2 1 3 3 -37.9 71.2 5.4 5 Ib 47.4 51.6 83.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2077 NM_012864 Huesken Mmp7 4316 UCUGCAUUUCCCUCAGUUUgu AAACUGAGGGAAAUGCAGA -0.9 -2.4 -0.7 1 0 3 -36.7 73.4 -8.7 6 II 42.1 55.8 116.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2078 NM_012864 Huesken Mmp7 4316 CAUUUCCCUCAGUUUGUCCac GGACAAACUGAGGGAAAUG -3.3 -2.1 2.2 -1 2 3 -36.7 83.1 10 5 II 47.4 55.7 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2079 NM_012864 Huesken Mmp7 4316 CCCUCAGUUUGUCCACUGCac GCAGUGGACAAACUGAGGG -3.4 -3.3 -3.7 -1 -1 3 -41.2 57.1 10.8 1 II 57.9 39.2 32.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2080 NM_012864 Huesken Mmp7 4316 UCAGUUUGUCCACUGCACUgg AGUGCAGUGGACAAACUGA -2.1 -2.4 -3.7 1 2 2 -38.9 67.3 -1.6 5 II 47.4 65.1 110.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2081 NM_012864 Huesken Mmp7 4316 CAGUUUGUCCACUGCACUGgu CAGUGCAGUGGACAAACUG -2.1 -2.1 -2.6 -1 0 2 -38.6 65.1 -2.1 3 II 52.6 52.5 100 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2082 NM_012864 Huesken Mmp7 4316 CCACUGCACUGGUGGCCUUcu AAGGCCACCAGUGCAGUGG -0.9 -3.3 -2.9 0 -2 4 -44.3 32.7 -6 0 III 63.2 27.5 22.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2083 NM_012864 Huesken Mmp7 4316 GCACUGGUGGCCUUCUUUGuu CAAAGAAGGCCACCAGUGC -2.1 -3.4 0.5 2 1 4 -40.9 51.6 -2.4 3 II 57.9 44 38.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2084 NM_012864 Huesken Mmp7 4316 ACUGGUGGCCUUCUUUGUUuu AACAAAGAAGGCCACCAGU -0.9 -2.2 0.5 2 2 4 -38.5 60.9 3.8 4 II 47.4 47.1 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2085 NM_012864 Huesken Mmp7 4316 UGGUGGCCUUCUUUGUUUUag AAAACAAAGAAGGCCACCA -0.9 -2.1 0.5 0 0 4 -36 76.1 -1 5 II 42.1 51.2 45.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2086 NM_012864 Huesken Mmp7 4316 UGGCCUUCUUUGUUUUAGAgu UCUAAAACAAAGAAGGCCA -2.4 -2.1 0.6 2 0 4 -34.2 81.4 -1.4 4 II 36.8 56.2 95.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2087 NM_012864 Huesken Mmp7 4316 CUUCUUUGUUUUAGAGUCGug CGACUCUAAAACAAAGAAG -2.4 -2.1 0.5 0 1 2 -31.2 73.8 -1.6 5 II 36.8 59.2 113.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2088 NM_012864 Huesken Mmp7 4316 CUUUGUUUUAGAGUCGUGAag UCACGACUCUAAAACAAAG -2.4 -2.1 3.2 0 -1 2 -32.5 79.5 -3.4 6 II 36.8 52.2 108 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2089 NM_012864 Huesken Mmp7 4316 UGUUUUAGAGUCGUGAAGGua CCUUCACGACUCUAAAACA -3.3 -2.1 4.8 0 4 2 -34.9 78.4 0 7 Ia 42.1 71.2 126.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2090 NM_012864 Huesken Mmp7 4316 UUUUAGAGUCGUGAAGGUAaa UACCUUCACGACUCUAAAA -1.3 -0.9 4.8 0 1 2 -34.1 68.2 2 8 II 36.8 58.1 110 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2091 NM_012864 Huesken Mmp7 4316 UUUAGAGUCGUGAAGGUAAaa UUACCUUCACGACUCUAAA -0.9 -0.9 4 1 0 2 -34.1 68.3 -6.3 8 II 36.8 59.6 130.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2092 NM_012864 Huesken Mmp7 4316 UUAGAGUCGUGAAGGUAAAau UUUACCUUCACGACUCUAA -0.9 -0.9 3.8 1 0 2 -34.1 59.7 -3.6 7 II 36.8 54.1 110 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2093 NM_012864 Huesken Mmp7 4316 GAGUCGUGAAGGUAAAAUUuc AAUUUUACCUUCACGACUC -0.9 -2.4 3.8 1 -2 2 -32.7 71.9 -4 4 III 36.8 45.4 76.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2094 NM_012864 Huesken Mmp7 4316 AGUCGUGAAGGUAAAAUUUcc AAAUUUUACCUUCACGACU -0.9 -2.1 3.8 2 0 2 -31.2 68.4 -3.5 5 II 31.6 52.2 74.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2095 NM_012864 Huesken Mmp7 4316 UCGUGAAGGUAAAAUUUCCua GGAAAUUUUACCUUCACGA -3.3 -2.4 0 1 2 2 -32.6 69.8 7.1 6 Ib 36.8 67.3 126.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2096 NM_012864 Huesken Mmp7 4316 GUGAAGGUAAAAUUUCCUAag UAGGAAAUUUUACCUUCAC -1.3 -2.2 -0.7 0 -1 2 -31.2 73.1 3.6 5 III 31.6 46.2 86.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2097 NM_012864 Huesken Mmp7 4316 AGGUAAAAUUUCCUAAGAUaa AUCUUAGGAAAUUUUACCU -1.1 -2.1 -0.6 1 1 2 -30.1 70.4 1.1 5 II 26.3 47 79.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2098 NM_012864 Huesken Mmp7 4316 GGUAAAAUUUCCUAAGAUAau UAUCUUAGGAAAUUUUACC -1.3 -3.3 0.8 0 -3 2 -29.3 67.8 -5.8 4 II 26.3 35.7 28.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2099 NM_012864 Huesken Mmp7 4316 AAAUUUCCUAAGAUAAUUCug GAAUUAUCUUAGGAAAUUU -2.4 -0.9 0.8 1 4 2 -26.9 99.6 9.4 8 Ia 21.1 74.5 116.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2100 NM_012864 Huesken Mmp7 4316 UUUCCUAAGAUAAUUCUGCgc GCAGAAUUAUCUUAGGAAA -3.4 -0.9 0.8 2 5 2 -31.6 89.9 7.1 8 Ia 31.6 83.7 131.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2101 NM_012864 Huesken Mmp7 4316 CCUAAGAUAAUUCUGCGCCug GGCGCAGAAUUAUCUUAGG -3.3 -3.3 0.9 -1 2 5 -36.5 69.1 15.9 5 II 47.4 58.3 134.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2102 NM_012864 Huesken Mmp7 4316 CUAAGAUAAUUCUGCGCCUgu AGGCGCAGAAUUAUCUUAG -2.1 -2.1 0.9 -1 0 5 -35.3 57.9 -8.3 4 II 42.1 50.1 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2103 NM_012864 Huesken Mmp7 4316 AAGAUAAUUCUGCGCCUGUuc ACAGGCGCAGAAUUAUCUU -2.2 -0.9 0.9 0 1 5 -36.2 64.2 -1.6 7 II 42.1 56 75.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2104 NM_012864 Huesken Mmp7 4316 AUAAUUCUGCGCCUGUUCCca GGAACAGGCGCAGAAUUAU -3.3 -1.1 3.6 2 5 5 -37.4 81.9 9.8 7 Ia 47.4 69.6 104.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2105 NM_012864 Huesken Mmp7 4316 UAAUUCUGCGCCUGUUCCCac GGGAACAGGCGCAGAAUUA -3.3 -1.3 3.6 1 5 5 -39.6 76 2.7 8 Ia 52.6 74.9 93.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2106 NM_012864 Huesken Mmp7 4316 AAUUCUGCGCCUGUUCCCAcu UGGGAACAGGCGCAGAAUU -2.1 -0.9 -0.7 2 3 5 -40.4 66 -0.8 6 II 52.6 52.9 46.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2107 NM_012864 Huesken Mmp7 4316 CUGUUCCCACUGAAGUGCGgu CGCACUUCAGUGGGAACAG -2.4 -2.1 -1.9 -1 1 3 -40.3 53.3 -4.6 1 II 57.9 50.5 91.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2108 NM_012864 Huesken Mmp7 4316 UGUUCCCACUGAAGUGCGGuc CCGCACUUCAGUGGGAACA -3.3 -2.1 -4.6 0 4 4 -41.5 56.1 -2.6 3 II 57.9 52.9 91.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2109 NM_012864 Huesken Mmp7 4316 CACUGAAGUGCGGUCACUUcu AAGUGACCGCACUUCAGUG -0.9 -2.1 -2.6 -1 -1 4 -39.2 47.5 -6 2 II 52.6 40.9 79.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2110 NM_012864 Huesken Mmp7 4316 ACUGAAGUGCGGUCACUUCuc GAAGUGACCGCACUUCAGU -2.4 -2.2 -7.1 2 2 4 -39.5 54.7 10.1 5 Ib 52.6 51.5 40.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2111 NM_012864 Huesken Mmp7 4316 CUGAAGUGCGGUCACUUCUcc AGAAGUGACCGCACUUCAG -2.1 -2.1 -7.3 1 -2 4 -39.4 61.7 2.2 4 II 52.6 52.5 32.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2112 NM_012864 Huesken Mmp7 4316 AGUGCGGUCACUUCUCCGGcu CCGGAGAAGUGACCGCACU -3.3 -2.1 -1.9 2 4 4 -43.3 58.9 0.7 3 II 63.2 57.9 94.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2113 NM_012864 Huesken Mmp7 4316 GGUCACUUCUCCGGCUUCCug GGAAGCCGGAGAAGUGACC -3.3 -3.3 0.7 2 1 5 -43.2 47 5.4 3 II 63.2 41.9 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2114 NM_012864 Huesken Mmp7 4316 CACUUCUCCGGCUUCCUGGga CCAGGAAGCCGGAGAAGUG -3.3 -2.1 -0.3 1 1 5 -42.8 69.7 -2 4 II 63.2 54.4 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2115 NM_012864 Huesken Mmp7 4316 ACUUCUCCGGCUUCCUGGGac CCCAGGAAGCCGGAGAAGU -3.3 -2.2 -0.6 2 4 5 -44 61.1 0.7 3 Ib 63.2 50.7 64.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2116 NM_012864 Huesken Mmp7 4316 GGCUUCCUGGGACAGUGGCag GCCACUGUCCCAGGAAGCC -3.4 -3.3 -0.3 1 1 3 -46 44 9.8 1 II 68.4 34.4 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2117 NM_012864 Huesken Mmp7 4316 UUCCUGGGACAGUGGCAGGgc CCUGCCACUGUCCCAGGAA -3.3 -0.9 -2.9 0 3 3 -44.7 50.8 2.3 4 II 63.2 60 67.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2118 NM_012864 Huesken Mmp7 4316 UGGGACAGUGGCAGGGCCAgg UGGCCCUGCCACUGUCCCA -2.1 -2.1 -3.1 -1 0 5 -48.1 32.3 -6 3 II 68.4 48.6 93.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2119 NM_012864 Huesken Mmp7 4316 AGUGGCAGGGCCAGGCAGCcu GCUGCCUGGCCCUGCCACU -3.4 -2.1 -3.2 1 3 5 -49.1 28 0.1 2 II 73.7 49.7 64.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2120 NM_025237 Huesken SOST 50964 GGCCGAGCGGCCUCGGUCCcg GGACCGAGGCCGCUCGGCC -3.3 -3.3 -6.9 2 0 6 -50.8 24 2.7 0 II 84.2 35.4 50.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2121 NM_025237 Huesken SOST 50964 GGCCUCGGUCCCGAAGUCCuu GGACUUCGGGACCGAGGCC -3.3 -3.3 -5.7 1 0 4 -47.1 29.4 2.7 1 II 73.7 37.7 53.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2122 NM_025237 Huesken SOST 50964 CCUCGGUCCCGAAGUCCUUga AAGGACUUCGGGACCGAGG -0.9 -3.3 -5.3 1 -2 4 -43.4 31.3 -8.6 0 III 63.2 32.2 58.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2123 NM_025237 Huesken SOST 50964 UCGGUCCCGAAGUCCUUGAgc UCAAGGACUUCGGGACCGA -2.4 -2.4 -1.8 1 -1 4 -42.5 59.2 -1.5 4 II 57.9 49.8 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2124 NM_025237 Huesken SOST 50964 CGGUCCCGAAGUCCUUGAGcu CUCAAGGACUUCGGGACCG -2.1 -2.4 0.1 -1 -1 4 -42.2 54.8 3.4 1 II 63.2 31.5 62.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2125 NM_025237 Huesken SOST 50964 GUCCCGAAGUCCUUGAGCUcc AGCUCAAGGACUUCGGGAC -2.1 -2.2 0 2 1 4 -42 50.7 -6.3 1 III 57.9 41.1 64.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2126 NM_025237 Huesken SOST 50964 CCCGAAGUCCUUGAGCUCCga GGAGCUCAAGGACUUCGGG -3.3 -3.3 -2.1 0 -1 4 -43.1 39.4 11.1 1 II 63.2 45.6 75 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2127 NM_025237 Huesken SOST 50964 CGAAGUCCUUGAGCUCCGAcu UCGGAGCUCAAGGACUUCG -2.4 -2.4 -2.9 -1 -2 3 -41.3 38 -5.8 0 III 57.9 31.1 61.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2128 NM_025237 Huesken SOST 50964 GAGCUCCGACUGGUUGUGGaa CCACAACCAGUCGGAGCUC -3.3 -2.4 -0.8 1 2 3 -43 45.1 2.3 2 II 63.2 39.8 80.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2129 NM_025237 Huesken SOST 50964 AGCGGGUGAGGCGCUUGCAcu UGCAAGCGCCUCACCCGCU -2.1 -2.1 -2.5 2 0 5 -46.4 32.4 -6.1 1 II 68.4 38.3 66.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2130 NM_025237 Huesken SOST 50964 GGUGAGGCGCUUGCACUUGca CAAGUGCAAGCGCCUCACC -2.1 -3.3 -1.7 1 0 5 -42.5 34.7 5.7 2 II 63.2 38 68.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2131 NM_025237 Huesken SOST 50964 ACUUGCACGAGGCCACCAGgc CUGGUGGCCUCGUGCAAGU -2.1 -2.2 -0.3 2 3 4 -43.7 50 2.4 5 Ib 63.2 48.9 52.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2132 NM_025237 Huesken SOST 50964 GAGGCCACCAGGCGCACCUug AGGUGCGCCUGGUGGCCUC -2.1 -2.4 -4.2 0 0 5 -48.5 37.2 -1.6 1 III 73.7 40.7 71.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2133 NM_025237 Huesken SOST 50964 CCAGGCGCACCUUGCGCGCgc GCGCGCAAGGUGCGCCUGG -3.4 -3.3 -8.2 -2 1 6 -47.7 26 6.1 0 II 78.9 38.4 41.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2134 NM_025237 Huesken SOST 50964 CGCACCUUGCGCGCGCGCGgc CGCGCGCGCGCAAGGUGCG -2.4 -2.4 -5.9 1 0 11 -47.5 34.2 -4.4 0 II 84.2 39.2 60.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2135 NM_025237 Huesken SOST 50964 CACCUUGCGCGCGCGCGGCgc GCCGCGCGCGCGCAAGGUG -3.4 -2.1 -4.6 1 1 13 -48.4 28.6 3.1 1 II 84.2 42.5 57.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2136 NM_025237 Huesken SOST 50964 GCGCGCGCGGCGCCUCACCac GGUGAGGCGCCGCGCGCGC -3.3 -3.4 -5.2 2 0 14 -51.1 15.5 7.5 -1 II 89.5 34.3 26 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2137 NM_025237 Huesken SOST 50964 GCGCGCGGCGCCUCACCACcg GUGGUGAGGCGCCGCGCGC -2.2 -3.4 -7.1 2 0 12 -49.6 17.7 2.7 -1 II 84.2 30 65.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2138 NM_025237 Huesken SOST 50964 CGCGGCGCCUCACCACCGGga CCGGUGGUGAGGCGCCGCG -3.3 -2.4 -7.1 0 0 9 -49.4 17.4 -2 -1 II 84.2 33.8 35.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2139 NM_025237 Huesken SOST 50964 CGCCUCACCACCGGGACACag GUGUCCCGGUGGUGAGGCG -2.2 -2.4 -0.6 0 -1 5 -46.7 32.5 0.7 2 II 73.7 36.9 62.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2140 NM_025237 Huesken SOST 50964 CCACCGGGACACAGCAGCUgc AGCUGCUGUGUCCCGGUGG -2.1 -3.3 -3.4 -1 -1 5 -46.1 24.7 -8.6 0 III 68.4 34.5 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2141 NM_025237 Huesken SOST 50964 CACGCGCUGCGCGCGGUAGcg CUACCGCGCGCAGCGCGUG -2.1 -2.1 -6.8 0 -1 8 -46.4 30.4 -4.4 0 II 78.9 32.3 50.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2142 NM_025237 Huesken SOST 50964 ACGCGCUGCGCGCGGUAGCgg GCUACCGCGCGCAGCGCGU -3.4 -2.2 -6.8 3 2 8 -47.7 28.8 7.5 1 II 78.9 44.8 51.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2143 NM_025237 Huesken SOST 50964 GUCGGGCCCACUAGGUCGCca GCGACCUAGUGGGCCCGAC -3.4 -2.2 -1.5 0 2 7 -47.1 32.5 5.5 0 II 73.7 41.4 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2144 NM_025237 Huesken SOST 50964 CCACUAGGUCGCCACCACUug AGUGGUGGCGACCUAGUGG -2.1 -3.3 -1.8 0 -2 4 -44.1 34.2 -5.9 1 III 63.2 38.6 78.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2145 NM_025237 Huesken SOST 50964 ACUAGGUCGCCACCACUUGcc CAAGUGGUGGCGACCUAGU -2.1 -2.2 -1.8 3 2 4 -41.7 49.5 0.1 4 Ib 57.9 53.3 64.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2146 NM_025237 Huesken SOST 50964 CACCACUUGCCGCGGCCGAug UCGGCCGCGGCAAGUGGUG -2.4 -2.1 -6.9 1 -2 10 -46.7 28.5 -3 1 III 73.7 29.1 66 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2147 NM_025237 Huesken SOST 50964 GCGGCCGAUGGCGUUGGGCag GCCCAACGCCAUCGGCCGC -3.4 -3.4 -2.1 0 2 7 -48.1 27.6 7.4 -1 II 78.9 34.5 64.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2148 NM_025237 Huesken SOST 50964 UGGCGUUGGGCAGCAGGCGcg CGCCUGCUGCCCAACGCCA -2.4 -2.1 0 3 3 4 -47.3 32.8 -2.4 3 II 73.7 58.5 64.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2149 NM_025237 Huesken SOST 50964 UUGGGCAGCAGGCGCGCCGgg CGGCGCGCCUGCUGCCCAA -2.4 -0.9 -3.5 0 4 9 -48.8 38.5 2.4 4 II 78.9 65.8 84.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2150 NM_025237 Huesken SOST 50964 GCAGGCGCGCCGGGCCGCAcu UGCGGCCCGGCGCGCCUGC -2.1 -3.4 -3.5 0 -1 15 -52.8 -2.8 -6.1 0 III 89.5 19.6 52.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2151 NM_025237 Huesken SOST 50964 GGGCCGCACUGGCCGGAGCac GCUCCGGCCAGUGCGGCCC -3.4 -3.3 -7 2 0 7 -51.2 23.8 9.8 -2 II 84.2 28.9 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2152 NM_025237 Huesken SOST 50964 CACACCAGCUCGGUGACCGgc CGGUCACCGAGCUGGUGUG -2.4 -2.1 -3.8 0 2 3 -44.3 48.2 -2 1 II 68.4 49.6 52.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2153 NM_025237 Huesken SOST 50964 CUCGGUGACCGGCUUGGCGcu CGCCAAGCCGGUCACCGAG -2.4 -2.1 -1.6 0 2 5 -45.7 41 2.7 0 II 73.7 47.1 59.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2154 NM_025237 Huesken SOST 50964 GGUGACCGGCUUGGCGCUGcg CAGCGCCAAGCCGGUCACC -2.1 -3.3 -1.6 0 1 5 -46.4 21.8 5.7 0 II 73.7 28.5 50.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2155 NM_025237 Huesken SOST 50964 GACCGGCUUGGCGCUGCGGca CCGCAGCGCCAAGCCGGUC -3.3 -2.4 -1.6 1 2 5 -47.9 25.5 -2.4 -1 II 78.9 35.5 51.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2156 NM_025237 Huesken SOST 50964 CGGCUUGGCGCUGCGGCACgg GUGCCGCAGCGCCAAGCCG -2.2 -2.4 -3.5 1 -1 5 -47.7 29.9 6.1 0 II 78.9 36.7 49.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2157 NM_025237 Huesken SOST 50964 GCUUGGCGCUGCGGCACGGcc CCGUGCCGCAGCGCCAAGC -3.3 -3.4 -3.8 0 2 5 -47.7 20.3 -2.4 0 II 78.9 28.9 50.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2158 NM_025237 Huesken SOST 50964 GCUGCGGCACGGCCCAUCGgu CGAUGGGCCGUGCCGCAGC -2.4 -3.4 -2.7 0 1 6 -48.1 33.7 2.4 1 II 78.9 39.3 51 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2159 NM_025237 Huesken SOST 50964 CUGCGGCACGGCCCAUCGGuc CCGAUGGGCCGUGCCGCAG -3.3 -2.1 -2.7 1 1 6 -48 25.8 -2 -1 II 78.9 41 54.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2160 NM_025237 Huesken SOST 50964 CCCAUCGGUCACGUAGCGGgu CCGCUACGUGACCGAUGGG -3.3 -3.3 0.2 -1 1 4 -43.9 39.4 0.3 2 II 68.4 39.9 64.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2161 NM_025237 Huesken SOST 50964 CCAUCGGUCACGUAGCGGGug CCCGCUACGUGACCGAUGG -3.3 -3.3 0.3 0 1 5 -43.9 44.6 -4.4 3 II 68.4 47 77.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2162 NM_025237 Huesken SOST 50964 CGGUCACGUAGCGGGUGAAgu UUCACCCGCUACGUGACCG -0.9 -2.4 -1.9 -2 -4 5 -42.6 31.5 -8.1 0 III 63.2 15.8 57.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2163 NM_025237 Huesken SOST 50964 GGUCACGUAGCGGGUGAAGug CUUCACCCGCUACGUGACC -2.1 -3.3 -1.9 0 0 5 -42.3 32.6 0.4 1 II 63.2 27.3 59.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2164 NM_025237 Huesken SOST 50964 GUAGCGGGUGAAGUGCAGCuc GCUGCACUUCACCCGCUAC -3.4 -2.2 0.3 0 3 5 -43 40.9 12 2 II 63.2 50.6 75.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2165 NM_025237 Huesken SOST 50964 GGGUGAAGUGCAGCUCGCGgc CGCGAGCUGCACUUCACCC -2.4 -3.3 -0.9 0 1 4 -44.3 28.9 -2.4 1 II 68.4 38.5 54.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2166 NM_025237 Huesken SOST 50964 GGUGAAGUGCAGCUCGCGGca CCGCGAGCUGCACUUCACC -3.3 -3.3 -0.9 1 3 5 -44.3 38.6 9.7 2 II 68.4 38.7 66.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2167 NM_025237 Huesken SOST 50964 GCAGCUGUACUCGGACACGuc CGUGUCCGAGUACAGCUGC -2.4 -3.4 -0.2 -1 1 3 -42.4 32.8 -2.4 1 II 63.2 40.7 54.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2168 NM_025237 Huesken SOST 50964 CAGCUGUACUCGGACACGUcu ACGUGUCCGAGUACAGCUG -2.2 -2.1 -0.2 2 -1 3 -41.2 42.3 -8.3 2 III 57.9 45 74.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2169 NM_025237 Huesken SOST 50964 AGCUGUACUCGGACACGUCuu GACGUGUCCGAGUACAGCU -2.4 -2.1 -0.2 1 2 3 -41.5 52.3 4.8 3 Ib 57.9 52.6 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2170 NM_025237 Huesken SOST 50964 CUGUACUCGGACACGUCUUug AAGACGUGUCCGAGUACAG -0.9 -2.1 -0.2 1 -2 3 -39 58.1 -5.9 4 II 52.6 45.9 87.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2171 NM_025237 Huesken SOST 50964 CUUUGGUCUCAAAGGGGUGgu CACCCCUUUGAGACCAAAG -2.1 -2.1 -2.2 -1 1 4 -38.6 52.6 -2.3 3 II 52.6 49.1 72.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2172 NM_025237 Huesken SOST 50964 GGUGGUGGGGAGGCCGCCCuc GGGCGGCCUCCCCACCACC -3.3 -3.3 -3.1 1 2 8 -52 21.2 9.7 0 II 84.2 40.8 64.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2173 NM_025237 Huesken SOST 50964 GGGAGGCCGCCCUCCGUUCuc GAACGGAGGGCGGCCUCCC -2.4 -3.3 -8 1 -1 8 -49.2 29.7 2.7 0 II 78.9 34.2 52.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2174 NM_025237 Huesken SOST 50964 UCUCCGCCCGGUUCAUGGUcu ACCAUGAACCGGGCGGAGA -2.2 -2.4 -1.3 2 2 8 -44.6 54.7 -1 2 II 63.2 47.7 69.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2175 NM_025237 Huesken SOST 50964 UCCGCCCGGUUCAUGGUCUug AGACCAUGAACCGGGCGGA -2.1 -2.4 -1.3 1 1 8 -44.6 48.2 -6.6 2 II 63.2 49.2 78.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2176 NM_025237 Huesken SOST 50964 CCCGGUUCAUGGUCUUGUUgu AACAAGACCAUGAACCGGG -0.9 -3.3 -0.7 0 -3 5 -39.2 54.6 -6 1 III 52.6 31.9 69.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2177 NM_025237 Huesken SOST 50964 CGGUUCAUGGUCUUGUUGUuc ACAACAAGACCAUGAACCG -2.2 -2.4 1.4 0 -2 3 -36.9 70 -6 4 III 47.4 44.1 52.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2178 NM_025237 Huesken SOST 50964 GUUGUUCUCCAGCUCCGGUgg ACCGGAGCUGGAGAACAAC -2.2 -2.2 -1.8 1 2 4 -41.8 59.5 3.1 1 II 57.9 42.3 83.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2179 NM_025237 Huesken SOST 50964 UGUUCUCCAGCUCCGGUGGag CCACCGGAGCUGGAGAACA -3.3 -2.1 -1.8 0 3 4 -44.1 68.2 3.1 4 Ib 63.2 58.3 86.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2180 NM_025237 Huesken SOST 50964 UCUCCAGCUCCGGUGGAGGcu CCUCCACCGGAGCUGGAGA -3.3 -2.4 -5.6 1 4 4 -46.7 44.3 0 3 II 68.4 54.2 68.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2181 NM_025237 Huesken SOST 50964 GCUCGGGGUACUCUCCGAGcu CUCGGAGAGUACCCCGAGC -2.1 -3.4 -6.5 1 2 5 -45.1 37 5.4 1 II 68.4 35.6 44.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2182 NM_025237 Huesken SOST 50964 CUCUCCGAGCUCGGGGAUGau CAUCCCCGAGCUCGGAGAG -2.1 -2.1 -3.6 -1 -1 5 -45 35 -4.4 1 II 68.4 38.2 50.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2183 NM_025237 Huesken SOST 50964 CCGAGCUCGGGGAUGAUUUcc AAAUCAUCCCCGAGCUCGG -0.9 -3.3 -2.5 1 -3 5 -41.3 50.1 -6.2 1 III 57.9 38.5 49.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2184 NM_025237 Huesken SOST 50964 UCCGUGGCAUCAUUCUUGAac UCAAGAAUGAUGCCACGGA -2.4 -2.4 0.7 0 0 3 -38.7 62.4 -3.8 6 II 47.4 50.5 68.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2185 NM_025237 Huesken SOST 50964 UGGCAUCAUUCUUGAACGCcu GCGUUCAAGAAUGAUGCCA -3.4 -2.1 -2.4 0 3 3 -37.3 61 10.8 3 II 47.4 58.2 93.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2186 NM_025237 Huesken SOST 50964 CAUCAUUCUUGAACGCCUGcc CAGGCGUUCAAGAAUGAUG -2.1 -2.1 -0.6 1 1 4 -36 61.8 -1.9 4 II 47.4 54.3 82.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2187 NM_025237 Huesken SOST 50964 CUUGAACGCCUGCCACCCCug GGGGUGGCAGGCGUUCAAG -3.3 -2.1 0 0 2 4 -44.8 36.3 10.5 2 II 68.4 48.9 48.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2188 NM_025237 Huesken SOST 50964 AACGCCUGCCACCCCUGGCcc GCCAGGGGUGGCAGGCGUU -3.4 -0.9 -5.1 3 4 4 -48.2 51.1 9.8 2 II 73.7 56.4 77.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2189 NM_025237 Huesken SOST 50964 CCUGCCACCCCUGGCCCUCca GAGGGCCAGGGGUGGCAGG -2.4 -3.3 -5.1 -1 0 5 -50.4 28.9 6.1 0 II 78.9 37.6 71.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2190 NM_025237 Huesken SOST 50964 GCCACCCCUGGCCCUCCACua GUGGAGGGCCAGGGGUGGC -2.2 -3.4 -3.4 0 0 5 -50.5 34.8 7.5 -1 II 78.9 28.1 52.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2191 NM_025237 Huesken SOST 50964 CACCCCUGGCCCUCCACUAca UAGUGGAGGGCCAGGGGUG -1.3 -2.1 -1.6 2 -3 5 -47.2 41.7 -10.5 0 III 68.4 34.1 72 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2192 NM_025237 Huesken SOST 50964 ACCCCUGGCCCUCCACUACac GUAGUGGAGGGCCAGGGGU -2.2 -2.2 -1.6 3 1 5 -47.3 46.2 10.5 2 II 68.4 44.2 63.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2193 NM_025237 Huesken SOST 50964 CCUGGCCCUCCACUACACGga CGUGUAGUGGAGGGCCAGG -2.4 -3.3 -1.6 -1 1 5 -45.2 35.7 0.4 -1 II 68.4 40.1 60.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2194 NM_025237 Huesken SOST 50964 CUGGCCCUCCACUACACGGaa CCGUGUAGUGGAGGGCCAG -3.3 -2.1 -1.6 0 1 5 -45.2 49 -2.1 -1 II 68.4 49.5 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2195 NM_005450 Huesken NOG 9241 CUGACAGCGCCACCGCAGCac GCUGCGGUGGCGCUGUCAG -3.4 -2.1 -2.8 0 0 5 -46.5 35.8 5.5 1 II 73.7 46.1 80.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2196 NM_005450 Huesken NOG 9241 CCACCGCAGCACCGUGAGGug CCUCACGGUGCUGCGGUGG -3.3 -3.3 -0.9 0 0 4 -46.4 24.8 0.4 0 II 73.7 31.7 70.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2197 NM_005450 Huesken NOG 9241 ACCGCAGCACCGUGAGGUGca CACCUCACGGUGCUGCGGU -2.1 -2.2 -3.8 0 2 4 -45.3 30.9 -2.4 1 II 68.4 37.3 56.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2198 NM_005450 Huesken NOG 9241 GAGGUGCACGGACUUGGACgg GUCCAAGUCCGUGCACCUC -2.2 -2.4 1.2 1 2 3 -43.1 44.1 12.1 1 II 63.2 39 55.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2199 NM_005450 Huesken NOG 9241 GUGCACGGACUUGGACGGCuu GCCGUCCAAGUCCGUGCAC -3.4 -2.2 0.9 0 2 4 -44.4 27.1 13.1 2 II 68.4 38.5 66.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2200 NM_005450 Huesken NOG 9241 GGACUUGGACGGCUUGCACac GUGCAAGCCGUCCAAGUCC -2.2 -3.3 1.5 1 2 4 -42.8 47.2 12.1 2 II 63.2 37.2 75.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2201 NM_005450 Huesken NOG 9241 UGGACGGCUUGCACACCAUgc AUGGUGUGCAAGCCGUCCA -1.1 -2.1 -3.6 0 0 4 -42.7 48.2 -8.9 3 II 57.9 48.5 86.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2202 NM_005450 Huesken NOG 9241 ACGGCUUGCACACCAUGCCcu GGCAUGGUGUGCAAGCCGU -3.3 -2.2 -3.8 3 3 4 -43.7 52.4 7.5 2 II 63.2 59.7 79.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2203 NM_005450 Huesken NOG 9241 GGCUUGCACACCAUGCCCUcg AGGGCAUGGUGUGCAAGCC -2.1 -3.3 -2.4 1 0 4 -44.5 46.2 -8.9 1 III 63.2 37.7 75.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2204 NM_005450 Huesken NOG 9241 CGGAGCACGAGCGCUUACUga AGUAAGCGCUCGUGCUCCG -2.1 -2.4 -2.7 0 -3 4 -42.6 43.5 -8.3 1 III 63.2 39.6 51 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2205 NM_005450 Huesken NOG 9241 CACGAGCGCUUACUGAAGCag GCUUCAGUAAGCGCUCGUG -3.4 -2.1 -2.5 0 1 4 -39.9 45.8 12.8 0 II 57.9 47.4 84.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2206 NM_005450 Huesken NOG 9241 GCGCUUACUGAAGCAGCUGcc CAGCUGCUUCAGUAAGCGC -2.1 -3.4 -2.5 1 0 4 -40.5 41.4 2.3 0 II 57.9 41.7 56.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2207 NM_005450 Huesken NOG 9241 CGCUUACUGAAGCAGCUGCcc GCAGCUGCUUCAGUAAGCG -3.4 -2.4 -2.5 0 -1 3 -40.5 57.1 10.1 2 II 57.9 43.3 63.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2208 NM_005450 Huesken NOG 9241 CGCGGCCAAAAGCGGCUGCcc GCAGCCGCUUUUGGCCGCG -3.4 -2.4 -3.7 -2 -1 7 -45.2 31.9 10.1 0 II 73.7 34 46.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2209 NM_005450 Huesken NOG 9241 AAAAGCGGCUGCCCAGGUCgu GACCUGGGCAGCCGCUUUU -2.4 -0.9 -1.7 2 4 5 -43.6 47.9 7.5 4 Ib 63.2 55.7 77.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2210 NM_005450 Huesken NOG 9241 AAGCGGCUGCCCAGGUCGUuc ACGACCUGGGCAGCCGCUU -2.2 -0.9 -1.6 2 2 5 -46.4 28.2 -11.3 1 II 68.4 41.1 51.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2211 NM_005450 Huesken NOG 9241 GCGGCUGCCCAGGUCGUUCca GAACGACCUGGGCAGCCGC -2.4 -3.4 -0.8 1 0 5 -46.7 38.7 12 1 II 73.7 38.8 59.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2212 NM_005450 Huesken NOG 9241 CGGCUGCCCAGGUCGUUCCac GGAACGACCUGGGCAGCCG -3.3 -2.4 -0.8 1 -1 4 -46.6 46.6 5.4 2 II 73.7 45 51.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2213 NM_005450 Huesken NOG 9241 CCAGGUCGUUCCACGCGUAca UACGCGUGGAACGACCUGG -1.3 -3.3 0 -1 -3 4 -42.6 26.5 -13 0 III 63.2 27.1 51.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2214 NM_005450 Huesken NOG 9241 UCGUUCCACGCGUACAGCAcg UGCUGUACGCGUGGAACGA -2.1 -2.4 -0.9 1 0 4 -41.5 55 -6.1 4 II 57.9 51.8 85.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2215 NM_005450 Huesken NOG 9241 UCCACGCGUACAGCACGGGgc CCCGUGCUGUACGCGUGGA -3.3 -2.4 -5.4 0 3 4 -44.8 38.3 -2.4 3 II 68.4 53.7 60.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2216 NM_005450 Huesken NOG 9241 GCGUACAGCACGGGGCAGAau UCUGCCCCGUGCUGUACGC -2.4 -3.4 -0.1 0 -3 6 -45.7 26 -3.4 3 III 68.4 24.9 61 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2217 NM_005450 Huesken NOG 9241 GUACAGCACGGGGCAGAAUgu AUUCUGCCCCGUGCUGUAC -1.1 -2.2 0.2 2 -1 6 -41.9 33.2 -1.3 2 III 57.9 30.7 51 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2218 NM_005450 Huesken NOG 9241 ACAGCACGGGGCAGAAUGUcu ACAUUCUGCCCCGUGCUGU -2.2 -2.2 0.2 1 1 6 -42.7 33.9 -8.9 3 II 57.9 38.9 60 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2219 NM_005450 Huesken NOG 9241 ACGGGGCAGAAUGUCUGCGac CGCAGACAUUCUGCCCCGU -2.4 -2.2 -5.2 2 4 6 -43.2 43.5 7.7 1 II 63.2 52.6 53 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2220 NM_005450 Huesken NOG 9241 CGGGGCAGAAUGUCUGCGAcc UCGCAGACAUUCUGCCCCG -2.4 -2.4 -5.2 -1 -3 6 -43.4 37.1 -5.8 0 III 63.2 34 47.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2221 NM_005450 Huesken NOG 9241 GGCAGAAUGUCUGCGACCAca UGGUCGCAGACAUUCUGCC -2.1 -3.3 -5.2 1 -2 3 -42 40.3 -3.1 0 III 57.9 29.8 40.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2222 NM_005450 Huesken NOG 9241 CAGAAUGUCUGCGACCACAgc UGUGGUCGCAGACAUUCUG -2.1 -2.1 -0.9 0 -3 3 -39.6 50.3 -5.4 4 II 52.6 45 57.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2223 NM_005450 Huesken NOG 9241 UGUCUGCGACCACAGCCACau GUGGCUGUGGUCGCAGACA -2.2 -2.1 -5.8 1 3 3 -44.1 45 7.5 3 II 63.2 53.1 83.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2224 NM_005450 Huesken NOG 9241 CUGCGACCACAGCCACAUCug GAUGUGGCUGUGGUCGCAG -2.4 -2.1 -6.8 0 -1 3 -43 38.7 10.1 -1 II 63.2 40.2 81.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2225 NM_005450 Huesken NOG 9241 UAACUUCCUCCGCAGCUUCuu GAAGCUGCGGAGGAAGUUA -2.4 -1.3 -1.5 1 3 4 -39.7 66.5 7.5 6 Ia 52.6 68.8 102 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2226 NM_005450 Huesken NOG 9241 UCCUCCGCAGCUUCUUGCUua AGCAAGAAGCUGCGGAGGA -2.1 -2.4 -2.5 0 1 4 -42.9 66.5 -3.3 3 II 57.9 51.6 97.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2227 NM_005450 Huesken NOG 9241 CGCAGCUUCUUGCUUAGGCgc GCCUAAGCAAGAAGCUGCG -3.4 -2.4 -2.5 1 1 3 -40.4 59.5 10.1 0 II 57.9 46.6 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2228 NM_005450 Huesken NOG 9241 GCUUCUUGCUUAGGCGCUGcu CAGCGCCUAAGCAAGAAGC -2.1 -3.4 -2.1 1 1 5 -40.4 46.1 0 1 II 57.9 39 62.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2229 NM_005450 Huesken NOG 9241 CUUGCUUAGGCGCUGCUUCuu GAAGCAGCGCCUAAGCAAG -2.4 -2.1 -2.1 1 1 5 -40.4 63.4 7.8 2 II 57.9 55.1 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2230 NM_005450 Huesken NOG 9241 UUAGGCGCUGCUUCUUGCCcu GGCAAGAAGCAGCGCCUAA -3.3 -0.9 -2.9 0 5 5 -41.6 65.5 8.1 4 II 57.9 73.2 91.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2231 NM_005450 Huesken NOG 9241 UAGGCGCUGCUUCUUGCCCug GGGCAAGAAGCAGCGCCUA -3.3 -1.3 -4 1 5 5 -44 61.1 15.2 2 II 63.2 67.6 93.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2232 NM_005450 Huesken NOG 9241 GCUUCUUGCCCUGGGCCAAgc UUGGCCCAGGGCAAGAAGC -0.9 -3.4 -2.7 1 -2 5 -44.4 42.1 -3.1 1 II 63.2 22.2 41.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2233 NM_005450 Huesken NOG 9241 CAAGCCCUCGGAGAACUCUag AGAGUUCUCCGAGGGCUUG -2.1 -2.1 -4.5 0 -1 4 -41.9 44.8 -6 1 III 57.9 44 55.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2234 NM_005450 Huesken NOG 9241 GAACUCUAGCCCUUUGAUCuc GAUCAAAGGGCUAGAGUUC -2.4 -2.4 -0.8 3 2 4 -37.4 68.8 5 4 II 47.4 52.2 78.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2235 NM_005450 Huesken NOG 9241 UCUAGCCCUUUGAUCUCGCuc GCGAGAUCAAAGGGCUAGA -3.4 -2.4 0.4 0 5 4 -40.1 63.4 7.1 5 II 52.6 63.5 96.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2236 NM_005450 Huesken NOG 9241 CCCCGACGGCCGCUGCCGCag GCGGCAGCGGCCGUCGGGG -3.4 -3.3 -7 1 1 7 -51.8 12.6 7.8 -2 II 89.5 28.4 70.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2237 NM_005450 Huesken NOG 9241 CCGCUGCCGCAGCAGCUGGuc CCAGCUGCUGCGGCAGCGG -3.3 -3.3 -9.1 1 -1 5 -48.5 26.5 2.7 0 II 78.9 35.5 78.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2238 NM_005450 Huesken NOG 9241 GCUGCCGCAGCAGCUGGUCca GACCAGCUGCUGCGGCAGC -2.4 -3.4 -7.4 0 1 5 -47.4 28.9 5.1 0 II 73.7 33.3 55.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2239 NM_005450 Huesken NOG 9241 GCAGCAGCUGGUCCAGCUCcg GAGCUGGACCAGCUGCUGC -2.4 -3.4 -4.6 0 1 2 -46.1 36.1 12.8 0 II 68.4 37.6 71.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2240 NM_005450 Huesken NOG 9241 GCUGGUCCAGCUCCGCCAGgu CUGGCGGAGCUGGACCAGC -2.1 -3.4 -2.7 0 1 5 -47.5 33.9 3.1 -1 II 73.7 30.7 58.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2241 NM_005450 Huesken NOG 9241 GCGAGGUGGCCAUGAAGCCug GGCUUCAUGGCCACCUCGC -3.3 -3.4 -5.7 1 1 4 -45.3 29.3 5.1 0 II 68.4 39.6 64.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2242 NM_005450 Huesken NOG 9241 UGGCCAUGAAGCCUGGGUCgu GACCCAGGCUUCAUGGCCA -2.4 -2.1 -5.9 2 3 4 -44.9 58.8 9.8 3 II 63.2 59.1 82.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2243 NM_005450 Huesken NOG 9241 CCCGAGCAGCGAGCGCAGCag GCUGCGCUCGCUGCUCGGG -3.4 -3.3 -1.3 0 -1 4 -48.2 15.6 8.1 -1 II 78.9 32.4 67.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2244 NM_005450 Huesken NOG 9241 GAGCAGCGAGCGCAGCAGCgu GCUGCUGCGCUCGCUGCUC -3.4 -2.4 -1.5 1 1 4 -46.8 26.1 10.2 0 II 73.7 39.4 78.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2245 NM_005450 Huesken NOG 9241 AGCAGCGAGCGCAGCAGCGuc CGCUGCUGCGCUCGCUGCU -2.4 -2.1 -2.6 1 3 4 -46.8 29.9 -4.9 2 II 73.7 47.8 73.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2246 NM_005450 Huesken NOG 9241 CAGCGAGCGCAGCAGCGUCuc GACGCUGCUGCGCUCGCUG -2.4 -2.1 -3.1 1 0 4 -45.9 27.3 10.1 0 II 73.7 40.9 70.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2247 NM_005450 Huesken NOG 9241 GCGCAGCAGCGUCUCGUUCag GAACGAGACGCUGCUGCGC -2.4 -3.4 -3.1 2 0 4 -43.8 37.9 17.9 0 II 68.4 33.5 74.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2248 NM_005450 Huesken NOG 9241 GCAGCAGCGUCUCGUUCAGau CUGAACGAGACGCUGCUGC -2.1 -3.4 -0.1 0 1 3 -42.2 34.1 3.1 1 II 63.2 26.9 46.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2249 NM_005450 Huesken NOG 9241 GUUCAGAUCCUUUUCCUUGgg CAAGGAAAAGGAUCUGAAC -2.1 -2.2 0.1 2 2 2 -34.5 75.2 8.1 5 II 42.1 56.9 95.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2250 NM_005450 Huesken NOG 9241 CCUUGGGGUCAAAGAUAGGgu CCUAUCUUUGACCCCAAGG -3.3 -3.3 -1.7 -2 0 4 -39.1 40.5 -2.3 2 II 52.6 39.9 89.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2251 NM_005450 Huesken NOG 9241 GGGUCAAAGAUAGGGUCUGgg CAGACCCUAUCUUUGACCC -2.1 -3.3 0.6 0 0 3 -39.5 41.8 0 3 II 52.6 37.8 88.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2252 NM_005450 Huesken NOG 9241 GGGUCUGGGUGUUCGAUGAgg UCAUCGAACACCCAGACCC -2.4 -3.3 1.5 1 -3 3 -42.2 55.8 -0.7 2 III 57.9 28.9 67.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2253 NM_005450 Huesken NOG 9241 GUCUGGGUGUUCGAUGAGGuc CCUCAUCGAACACCCAGAC -3.3 -2.2 1.5 1 1 3 -41 42.6 -2.4 2 II 57.9 43.6 79.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2254 NM_005450 Huesken NOG 9241 UCUGGGUGUUCGAUGAGGUcc ACCUCAUCGAACACCCAGA -2.2 -2.4 2 1 3 3 -41 54 -6.6 5 II 52.6 56 101.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2255 NM_005450 Huesken NOG 9241 UGUUCGAUGAGGUCCACCAgg UGGUGGACCUCAUCGAACA -2.1 -2.1 -2.3 1 1 2 -41 71 -3.8 6 II 52.6 61 96.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2256 NM_005450 Huesken NOG 9241 UUCGAUGAGGUCCACCAGGgg CCUGGUGGACCUCAUCGAA -3.3 -0.9 -2.4 1 3 2 -42.1 51.6 2.8 4 Ib 57.9 70.5 81.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2257 NM_005450 Huesken NOG 9241 GGGGCAGGUUGUCGCUGGGug CCCAGCGACAACCUGCCCC -3.3 -3.3 -0.9 -1 1 5 -47.2 28 5.4 0 II 73.7 27.9 68.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2258 NM_005450 Huesken NOG 9241 UUGUCGCUGGGUGCCGGGCgg GCCCGGCACCCAGCGACAA -3.4 -0.9 -1 1 4 7 -47.6 50.7 10.4 3 II 73.7 61 88.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2259 NM_005450 Huesken NOG 9241 UCGCUGGGUGCCGGGCGGAug UCCGCCCGGCACCCAGCGA -2.4 -2.4 -1.7 0 0 9 -50.5 15.5 -8.5 3 II 78.9 39.1 72 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2260 NM_005450 Huesken NOG 9241 CGCUGGGUGCCGGGCGGAUgu AUCCGCCCGGCACCCAGCG -1.1 -2.4 -1 -1 -3 9 -49.2 12.9 -8.3 0 III 78.9 17.3 42.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2261 NM_005450 Huesken NOG 9241 GGGUGCCGGGCGGAUGUGGag CCACAUCCGCCCGGCACCC -3.3 -3.3 -0.2 1 0 9 -48.9 22.5 -2.4 1 II 78.9 29.2 51.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2262 NM_005450 Huesken NOG 9241 GCCGGGCGGAUGUGGAGAUag AUCUCCACAUCCGCCCGGC -1.1 -3.4 -0.2 0 -2 9 -46 20.3 -4 0 III 68.4 18.7 60.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2263 NM_005450 Huesken NOG 9241 GGGCGGAUGUGGAGAUAGUgc ACUAUCUCCACAUCCGCCC -2.2 -3.3 4.4 1 -2 6 -42.5 29.8 -6.6 0 III 57.9 26.3 52.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2264 NM_005450 Huesken NOG 9241 GGAGAUAGUGCUGGCCGCCgg GGCGGCCAGCACUAUCUCC -3.3 -3.3 -1.7 -1 2 7 -45.7 30.8 10.8 1 II 68.4 44.6 87.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2265 NM_005450 Huesken NOG 9241 GAUAGUGCUGGCCGCCGGCcg GCCGGCGGCCAGCACUAUC -3.4 -2.4 -1.8 -1 3 10 -47 37.7 7.5 2 II 73.7 45.2 82.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2266 NM_007019 Huesken UBE2C 11065 UUCCAGAGCUCGGCAGCAUgu AUGCUGCCGAGCUCUGGAA -1.1 -0.9 -1.8 2 1 4 -43.1 42.6 -3.6 4 II 57.9 50.1 84.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2267 NM_007019 Huesken UBE2C 11065 UCCAGAGCUCGGCAGCAUGug CAUGCUGCCGAGCUCUGGA -2.1 -2.4 -1.8 0 1 4 -44.3 45.1 2.4 3 II 63.2 53.7 90.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2268 NM_007019 Huesken UBE2C 11065 AGCUCGGCAGCAUGUGUGUuc ACACACAUGCUGCCGAGCU -2.2 -2.1 -1.8 0 0 4 -42.8 48.8 -6.3 3 II 57.9 39.8 78 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2269 NM_007019 Huesken UBE2C 11065 CUCGGCAGCAUGUGUGUUCaa GAACACACAUGCUGCCGAG -2.4 -2.1 2.4 -1 -1 4 -40.6 51.5 5.4 3 II 57.9 49.3 89.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2270 NM_007019 Huesken UBE2C 11065 UCGGCAGCAUGUGUGUUCAag UGAACACACAUGCUGCCGA -2.1 -2.4 2.1 0 0 4 -40.6 58.7 1.6 5 II 52.6 47.5 86.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2271 NM_007019 Huesken UBE2C 11065 AUGUGUGUUCAAGGGACUAuc UAGUCCCUUGAACACACAU -1.3 -1.1 1.6 0 0 3 -37 56.5 -1.5 5 II 42.1 48.4 76.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2272 NM_007019 Huesken UBE2C 11065 UUCAAGGGACUAUCAAUGUug ACAUUGAUAGUCCCUUGAA -2.2 -0.9 1.9 0 1 3 -34.9 70.3 -1.3 8 II 36.8 65 90.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2273 NM_007019 Huesken UBE2C 11065 UCAAGGGACUAUCAAUGUUgg AACAUUGAUAGUCCCUUGA -0.9 -2.4 1.9 1 1 3 -34.9 65.2 3.8 6 II 36.8 56.1 93.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2274 NM_007019 Huesken UBE2C 11065 CUAUCAAUGUUGGGUUCUCcu GAGAACCCAACAUUGAUAG -2.4 -2.1 1.8 -1 1 3 -34.9 59.9 5.4 4 II 42.1 49.2 66.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2275 NM_007019 Huesken UBE2C 11065 AUCAAUGUUGGGUUCUCCUag AGGAGAACCCAACAUUGAU -2.1 -1.1 -1.1 1 3 3 -36.9 78.7 1.1 5 II 42.1 63.1 94.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2276 NM_007019 Huesken UBE2C 11065 AAUGUUGGGUUCUCCUAGAag UCUAGGAGAACCCAACAUU -2.4 -0.9 -1.1 2 1 3 -37.1 66.7 -6.1 5 II 42.1 54 88.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2277 NM_007019 Huesken UBE2C 11065 UGUUGGGUUCUCCUAGAAGgc CUUCUAGGAGAACCCAACA -2.1 -2.1 -1.1 0 3 3 -38.1 66.3 2.4 5 II 47.4 59.3 86.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2278 NM_007019 Huesken UBE2C 11065 UUGGGUUCUCCUAGAAGGCuc GCCUUCUAGGAGAACCCAA -3.4 -0.9 -1.1 0 4 3 -40.5 60.6 5.5 4 Ib 52.6 70.4 92.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2279 NM_007019 Huesken UBE2C 11065 GUUCUCCUAGAAGGCUCUGga CAGAGCCUUCUAGGAGAAC -2.1 -2.2 -0.9 0 2 3 -39.6 51 2.3 3 II 52.6 41.2 75.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2280 NM_007019 Huesken UBE2C 11065 UCCUAGAAGGCUCUGGAUGga CAUCCAGAGCCUUCUAGGA -2.1 -2.4 -0.7 1 2 3 -40.9 62.7 8.1 6 Ib 52.6 59.5 78.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2281 NM_007019 Huesken UBE2C 11065 UAGAAGGCUCUGGAUGGAGag CUCCAUCCAGAGCCUUCUA -2.1 -1.3 -0.5 0 3 3 -40.9 51.4 2.7 7 Ib 52.6 62.2 81.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2282 NM_007019 Huesken UBE2C 11065 CUGGAUGGAGAGCAGAAUGgu CAUUCUGCUCUCCAUCCAG -2.1 -2.1 1.4 -1 -1 2 -39.5 50.7 5.4 3 II 52.6 51.5 79.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2283 NM_007019 Huesken UBE2C 11065 GGAGAGCAGAAUGGUCCUGac CAGGACCAUUCUGCUCUCC -2.1 -3.3 -1.2 0 1 2 -41.8 35 8 1 II 57.9 36.2 45.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2284 NM_007019 Huesken UBE2C 11065 AGCAGAAUGGUCCUGACAUca AUGUCAGGACCAUUCUGCU -1.1 -2.1 -1.3 2 1 2 -39.4 56.4 -1.6 3 II 47.4 45.8 56.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2285 NM_007019 Huesken UBE2C 11065 GCAGAAUGGUCCUGACAUCau GAUGUCAGGACCAUUCUGC -2.4 -3.4 -1.3 1 0 2 -39.7 39.1 5.4 2 II 52.6 37.3 48.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2286 NM_007019 Huesken UBE2C 11065 GAAUGGUCCUGACAUCAUAca UAUGAUGUCAGGACCAUUC -1.3 -2.4 0.6 2 -2 2 -36.6 58.2 -1.4 4 II 42.1 39.6 32.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2287 NM_007019 Huesken UBE2C 11065 GGUCCUGACAUCAUACAGGgc CCUGUAUGAUGUCAGGACC -3.3 -3.3 -4.5 2 2 2 -39.8 55.6 -2.6 2 II 52.6 49.4 42 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2288 NM_007019 Huesken UBE2C 11065 CCUGACAUCAUACAGGGCAga UGCCCUGUAUGAUGUCAGG -2.1 -3.3 -3.7 0 -2 4 -40.7 47.1 -0.7 3 III 52.6 42.6 50.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2289 NM_007019 Huesken UBE2C 11065 ACAUCAUACAGGGCAGACCac GGUCUGCCCUGUAUGAUGU -3.3 -2.2 -0.7 3 3 4 -40.8 61.1 7.4 6 Ia 52.6 60.8 55.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2290 NM_007019 Huesken UBE2C 11065 CAUCAUACAGGGCAGACCAcu UGGUCUGCCCUGUAUGAUG -2.1 -2.1 -0.7 0 -1 4 -40.7 53.2 -0.7 4 II 52.6 46.6 28.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2291 NM_007019 Huesken UBE2C 11065 UCAUACAGGGCAGACCACUuu AGUGGUCUGCCCUGUAUGA -2.1 -2.4 -0.7 1 1 4 -41.8 47.9 -3.6 7 II 52.6 60.4 61.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2292 NM_007019 Huesken UBE2C 11065 GGCAGACCACUUUUCCUUCag GAAGGAAAAGUGGUCUGCC -2.4 -3.3 0.1 0 0 3 -39 59.2 12.8 2 II 52.6 39.2 63.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2293 NM_007019 Huesken UBE2C 11065 GACCACUUUUCCUUCAGGAug UCCUGAAGGAAAAGUGGUC -2.4 -2.4 -2.1 2 0 2 -38 62.9 -3.4 2 III 47.4 38.6 71.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2294 NM_007019 Huesken UBE2C 11065 CACUUUUCCUUCAGGAUGUcc ACAUCCUGAAGGAAAAGUG -2.2 -2.1 -2.4 0 -2 2 -35.5 70 -10.9 4 II 42.1 48.5 46.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2295 NM_007019 Huesken UBE2C 11065 UUCCUUCAGGAUGUCCAGGca CCUGGACAUCCUGAAGGAA -3.3 -0.9 -2.4 2 4 2 -40.5 68.4 7.7 4 Ib 52.6 67.1 74.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2296 NM_007019 Huesken UBE2C 11065 UCCUUCAGGAUGUCCAGGCau GCCUGGACAUCCUGAAGGA -3.4 -2.4 -1.6 1 3 3 -43 65.4 7.4 5 Ib 57.9 66.7 85.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2297 NM_007019 Huesken UBE2C 11065 CCUUCAGGAUGUCCAGGCAua UGCCUGGACAUCCUGAAGG -2.1 -3.3 -1 -1 -2 3 -42.7 46.7 -0.3 1 III 57.9 27.3 49.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2298 NM_007019 Huesken UBE2C 11065 AGGAUGUCCAGGCAUAUGUua ACAUAUGCCUGGACAUCCU -2.2 -2.1 -1 3 0 3 -39.7 69.7 -1.6 6 II 47.4 56.9 75.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2299 NM_007019 Huesken UBE2C 11065 GGCAUAUGUUACCCUGGGUgu ACCCAGGGUAACAUAUGCC -2.2 -3.3 -1.5 1 -1 3 -40.6 54.7 -1.6 2 II 52.6 32.2 39.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2300 NM_007019 Huesken UBE2C 11065 UUACCCUGGGUGUCCACGUug ACGUGGACACCCAGGGUAA -2.2 -0.9 -1.8 3 3 3 -42.9 60.5 -4 4 II 57.9 66.4 83 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2301 NM_007019 Huesken UBE2C 11065 GGGUGUCCACGUUGGGGUGau CACCCCAACGUGGACACCC -2.1 -3.3 -1.1 -1 0 4 -44.9 41.8 3 -1 II 68.4 28.3 11.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2302 NM_007019 Huesken UBE2C 11065 GUCCACGUUGGGGUGAUAGca CUAUCACCCCAACGUGGAC -2.1 -2.2 -1.9 1 1 4 -40.9 51.6 5 2 II 57.9 40.6 77.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2303 NM_007019 Huesken UBE2C 11065 UCCACGUUGGGGUGAUAGCag GCUAUCACCCCAACGUGGA -3.4 -2.4 -1.9 1 2 4 -42.1 60.6 7.4 3 II 57.9 58.2 89.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2304 NM_007019 Huesken UBE2C 11065 CGUUGGGGUGAUAGCAGGGcg CCCUGCUAUCACCCCAACG -3.3 -2.4 2.9 -2 1 4 -42.9 39.5 0.7 2 II 63.2 42.2 53.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2305 NM_007019 Huesken UBE2C 11065 GUUGGGGUGAUAGCAGGGCgu GCCCUGCUAUCACCCCAAC -3.4 -2.2 1.1 1 3 4 -43.9 35.2 7.4 3 II 63.2 49.3 63.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2306 NM_007019 Huesken UBE2C 11065 UAGCAGGGCGUGAGGAACUuc AGUUCCUCACGCCCUGCUA -2.1 -1.3 0.8 1 1 5 -43.1 41 -3.9 5 II 57.9 60.7 84.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2307 NM_007019 Huesken UBE2C 11065 AGCAGGGCGUGAGGAACUUca AAGUUCCUCACGCCCUGCU -0.9 -2.1 0.8 1 0 5 -42.7 29.9 -4 3 II 57.9 36 51 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2308 NM_007019 Huesken UBE2C 11065 GCAGGGCGUGAGGAACUUCac GAAGUUCCUCACGCCCUGC -2.4 -3.4 0.8 0 0 5 -43 26.8 9.7 1 II 63.2 36.9 40.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2309 NM_007019 Huesken UBE2C 11065 GUGAGGAACUUCACUGUGGgc CCACAGUGAAGUUCCUCAC -3.3 -2.2 -2 1 1 2 -39.1 51.9 -4.9 3 II 52.6 52.3 74.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2310 NM_007019 Huesken UBE2C 11065 GAGGAACUUCACUGUGGGCgc GCCCACAGUGAAGUUCCUC -3.4 -2.4 1.8 -1 2 4 -41.5 45.5 10.1 1 II 57.9 39.2 46.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2311 NM_007019 Huesken UBE2C 11065 GGAACUUCACUGUGGGCGCau GCGCCCACAGUGAAGUUCC -3.4 -3.3 -0.6 0 2 6 -42.8 50.7 7.4 2 II 63.2 45.1 70.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2312 NM_007019 Huesken UBE2C 11065 ACUUCACUGUGGGCGCAUUgu AAUGCGCCCACAGUGAAGU -0.9 -2.2 -0.6 2 0 6 -40.3 52.5 -4 4 II 52.6 35.9 57.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2313 NM_007019 Huesken UBE2C 11065 UUCACUGUGGGCGCAUUGUaa ACAAUGCGCCCACAGUGAA -2.2 -0.9 -0.6 1 1 6 -40.3 66.6 -6.3 7 II 52.6 60.2 93.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2314 NM_007019 Huesken UBE2C 11065 GUGGGCGCAUUGUAAGGGUag ACCCUUACAAUGCGCCCAC -2.2 -2.2 2.5 0 0 6 -41.6 38.3 -4 1 III 57.9 36.4 47.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2315 NM_007019 Huesken UBE2C 11065 CGCAUUGUAAGGGUAGCCAcu UGGCUACCCUUACAAUGCG -2.1 -2.4 -0.4 -1 -2 3 -39.5 56.1 -3.4 4 III 52.6 39.3 61.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2316 NM_007019 Huesken UBE2C 11065 GCAUUGUAAGGGUAGCCACug GUGGCUACCCUUACAAUGC -2.2 -3.4 -0.2 1 1 3 -39.3 56.9 7.4 4 II 52.6 44.4 87.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2317 NM_007019 Huesken UBE2C 11065 CAUUGUAAGGGUAGCCACUgg AGUGGCUACCCUUACAAUG -2.1 -2.1 -0.4 -1 -1 3 -38 59 -5.5 4 II 47.4 48.9 76.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2318 NM_007019 Huesken UBE2C 11065 UGUAAGGGUAGCCACUGGGga CCCAGUGGCUACCCUUACA -3.3 -2.1 -0.4 0 4 3 -42.6 57.1 2.8 7 Ib 57.9 65.4 85.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2319 NM_007019 Huesken UBE2C 11065 GUAAGGGUAGCCACUGGGGaa CCCCAGUGGCUACCCUUAC -3.3 -2.2 0.4 0 3 4 -43.8 41 -7.3 3 II 63.2 49.3 67.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2320 NM_007019 Huesken UBE2C 11065 GUAGCCACUGGGGAACUCUag AGAGUUCCCCAGUGGCUAC -2.1 -2.2 0.2 0 0 4 -42.8 45.3 -4 3 III 57.9 45.8 87 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2321 NM_007019 Huesken UBE2C 11065 UAGCCACUGGGGAACUCUAgc UAGAGUUCCCCAGUGGCUA -1.3 -1.3 0.2 2 0 4 -41.9 51.2 -6.3 4 II 52.6 50 67.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2322 NM_007019 Huesken UBE2C 11065 GCCACUGGGGAACUCUAGCga GCUAGAGUUCCCCAGUGGC -3.4 -3.4 -0.1 1 1 4 -44 49.4 14.4 1 II 63.2 41.8 69 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2323 NM_007019 Huesken UBE2C 11065 CCACUGGGGAACUCUAGCGag CGCUAGAGUUCCCCAGUGG -2.4 -3.3 -1.1 1 1 4 -43 45.6 -2.1 2 II 63.2 50.1 86.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2324 NM_007019 Huesken UBE2C 11065 GAACUCUAGCGAGAGCUUAua UAAGCUCUCGCUAGAGUUC -1.3 -2.4 -4 3 -2 3 -38 50.2 -3.8 4 II 47.4 38.2 60.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2325 NM_007019 Huesken UBE2C 11065 UCUAGCGAGAGCUUAUACCuc GGUAUAAGCUCUCGCUAGA -3.3 -2.4 -1.8 1 4 3 -38.3 75.1 7.4 6 II 47.4 70 91.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2326 NM_007019 Huesken UBE2C 11065 CUAGCGAGAGCUUAUACCUca AGGUAUAAGCUCUCGCUAG -2.1 -2.1 -1.8 -1 0 3 -38 59.6 -5.3 2 III 47.4 53.8 92.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2327 NM_007019 Huesken UBE2C 11065 AGCGAGAGCUUAUACCUCAgg UGAGGUAUAAGCUCUCGCU -2.1 -2.1 -2.1 2 -1 3 -39.1 49.6 -1.1 4 II 47.4 50 80.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2328 NM_007019 Huesken UBE2C 11065 GCGAGAGCUUAUACCUCAGgu CUGAGGUAUAAGCUCUCGC -2.1 -3.4 -2.1 0 0 3 -39.1 48.1 2.7 1 II 52.6 36.2 75.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2329 NM_007019 Huesken UBE2C 11065 GAGAGCUUAUACCUCAGGUcu ACCUGAGGUAUAAGCUCUC -2.2 -2.4 -1.2 1 1 2 -38.8 67 0.7 2 III 47.4 44.3 80.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2330 NM_007019 Huesken UBE2C 11065 GAGCUUAUACCUCAGGUCUuc AGACCUGAGGUAUAAGCUC -2.1 -2.4 -0.4 1 -1 2 -38.8 66.4 -0.9 4 II 47.4 47.5 71.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2331 NM_007019 Huesken UBE2C 11065 AGCUUAUACCUCAGGUCUUca AAGACCUGAGGUAUAAGCU -0.9 -2.1 -0.4 2 0 2 -37.3 60.3 -8.9 5 II 42.1 46.1 46.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2332 NM_007019 Huesken UBE2C 11065 CCUCAGGUCUUCAUAUACUgu AGUAUAUGAAGACCUGAGG -2.1 -3.3 1.8 1 -1 2 -36.5 55.3 -5.9 3 III 42.1 43.8 77.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2333 NM_007019 Huesken UBE2C 11065 CUCAGGUCUUCAUAUACUGuu CAGUAUAUGAAGACCUGAG -2.1 -2.1 0.3 0 0 2 -35.3 64.8 -4.4 3 II 42.1 54.6 82.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2334 NM_007019 Huesken UBE2C 11065 UCAGGUCUUCAUAUACUGUuc ACAGUAUAUGAAGACCUGA -2.2 -2.4 -0.2 0 2 2 -35.4 74.3 1.1 5 II 36.8 60.4 88.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2335 NM_007019 Huesken UBE2C 11065 AGGUCUUCAUAUACUGUUCca GAACAGUAUAUGAAGACCU -2.4 -2.1 0.8 2 1 2 -34.2 87.9 10.1 5 Ib 36.8 59.9 86.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2336 NM_007019 Huesken UBE2C 11065 CUUCAUAUACUGUUCCAGCug GCUGGAACAGUAUAUGAAG -3.4 -2.1 -1.2 0 2 2 -35.1 75.2 10.4 3 II 42.1 61.9 90.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2337 NM_007019 Huesken UBE2C 11065 UUCAUAUACUGUUCCAGCUgc AGCUGGAACAGUAUAUGAA -2.1 -0.9 -1.5 2 2 2 -35.1 89.4 -1 6 II 36.8 69.4 97.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2338 NM_007019 Huesken UBE2C 11065 UAUACUGUUCCAGCUGCUCca GAGCAGCUGGAACAGUAUA -2.4 -1.3 -1.5 0 4 2 -38.6 73.1 5.1 6 Ia 47.4 70.8 85.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2339 NM_007019 Huesken UBE2C 11065 ACUGUUCCAGCUGCUCCAUgg AUGGAGCAGCUGGAACAGU -1.1 -2.2 -0.8 1 1 2 -41.4 53.8 -3.3 4 II 52.6 40.7 84.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2340 NM_007019 Huesken UBE2C 11065 CCAGCUGCUCCAUGGAUGGuc CCAUCCAUGGAGCAGCUGG -3.3 -3.3 -1.2 -2 0 2 -43.8 41.8 -4.4 1 II 63.2 43.5 80.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2341 NM_007019 Huesken UBE2C 11065 CAGCUGCUCCAUGGAUGGUcc ACCAUCCAUGGAGCAGCUG -2.2 -2.1 -1.7 0 -1 2 -42.7 42.3 -0.7 0 III 57.9 33.1 62.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2342 NM_002559 Huesken P2RX3 5024 UGGGUUGGUCAAAGCCGCGau CGCGGCUUUGACCAACCCA -2.4 -2.1 -1 -1 3 6 -42.7 43.6 -0.3 3 II 63.2 62.5 84.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2343 NM_002559 Huesken P2RX3 5024 CACUCCCACAGAAGUAAAGgc CUUUACUUCUGUGGGAGUG -2.1 -2.1 -4 -1 -1 3 -36.7 60 -4.6 2 II 47.4 41 67.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2344 NM_002559 Huesken P2RX3 5024 AAGCCUUCAGGAGGGUGCGgu CGCACCCUCCUGAAGGCUU -2.4 -0.9 -0.7 2 4 3 -43.8 48.6 0 3 Ib 63.2 56.4 67.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2345 NM_002559 Huesken P2RX3 5024 AACCUGAAGUUGUAGCCUGgg CAGGCUACAACUUCAGGUU -2.1 -0.9 0.9 3 3 3 -37.7 57.9 0 5 Ib 47.4 60.2 95.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2346 NM_002559 Huesken P2RX3 5024 AAACGCUGUCGAGCCGGGUga ACCCGGCUCGACAGCGUUU -2.2 -0.9 -1.7 3 3 6 -43.4 40.2 -4 3 II 63.2 50.2 94.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2347 NM_002559 Huesken P2RX3 5024 UCGAGCCGGGUGAAGGAGUau ACUCCUUCACCCGGCUCGA -2.2 -2.4 0.7 1 0 6 -44.7 36.7 -6.6 3 II 63.2 49.4 80.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2348 NM_002559 Huesken P2RX3 5024 CCCAGGCCUUGUCCAAGUCgc GACUUGGACAAGGCCUGGG -2.4 -3.3 -0.5 -1 -1 4 -43.5 42.1 10.8 0 II 63.2 35 93 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2349 NM_002559 Huesken P2RX3 5024 UUGACCACGUCCCCUACCCgc GGGUAGGGGACGUGGUCAA -3.3 -0.9 -0.6 1 4 4 -44.3 63.5 5.1 5 Ib 63.2 72 94.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2350 NM_002559 Huesken P2RX3 5024 AGAUGGGGCAGAAAGGGUCcu GACCCUUUCUGCCCCAUCU -2.4 -2.1 1.8 2 3 5 -42.7 45.1 4.8 5 II 57.9 57.6 65.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2351 NM_002559 Huesken P2RX3 5024 UGUCCGGGUGGAAGCGGCAgg UGCCGCUUCCACCCGGACA -2.1 -2.1 -2.1 0 1 5 -46.6 31.3 -6.3 3 II 68.4 46.4 93.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2352 NM_002559 Huesken P2RX3 5024 AACGGAUGCUGUUCUUGAUga AUCAAGAACAGCAUCCGUU -1.1 -0.9 1.2 3 1 3 -36.1 69.1 -1 4 II 42.1 44.5 70.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2353 NM_002559 Huesken P2RX3 5024 UUGAUGAAAAUAGUGAAGUuc ACUUCACUAUUUUCAUCAA -2.2 -0.9 4.6 0 2 1 -30.1 83 -1.6 8 II 26.3 75.1 92.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2354 NM_002559 Huesken P2RX3 5024 CAUCAUGAUGGGCGUUUCCac GGAAACGCCCAUCAUGAUG -3.3 -2.1 -1.1 -1 1 5 -38.6 57.8 10.5 4 II 52.6 51.7 74.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2355 NM_002559 Huesken P2RX3 5024 GUUUCCACUGUGUCCACCUcc AGGUGGACACAGUGGAAAC -2.1 -2.2 0.3 0 1 2 -40.1 65.8 -4 4 II 52.6 51.2 91.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2356 NM_002559 Huesken P2RX3 5024 CCACCUCCGUGGGGCACCAgc UGGUGCCCCACGGAGGUGG -2.1 -3.3 -3.9 0 -2 5 -48.4 20.9 -5.8 -1 III 73.7 25.1 13.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2357 NM_002559 Huesken P2RX3 5024 GCCCGCACUGGCUGUCUGAua UCAGACAGCCAGUGCGGGC -2.4 -3.4 -2.9 0 -3 6 -46.4 31.2 -6.1 0 III 68.4 22.4 23.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2358 NM_002559 Huesken P2RX3 5024 ACACAGCGGUAUUUCUCCUca AGGAGAAAUACCGCUGUGU -2.1 -2.2 -0.4 3 3 4 -38.5 59.2 6.4 4 II 47.4 48.9 71.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2359 NM_002559 Huesken P2RX3 5024 CACAGCGGUAUUUCUCCUCac GAGGAGAAAUACCGCUGUG -2.4 -2.1 -0.4 -1 0 4 -38.7 62.8 8.4 4 II 52.6 53.7 67.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2360 NM_002559 Huesken P2RX3 5024 CCUCACUCUCUGGGCAGAAuc UUCUGCCCAGAGAGUGAGG -0.9 -3.3 -1 0 -3 4 -42.8 33 -3.1 1 III 57.9 25.1 44.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2361 NM_002559 Huesken P2RX3 5024 UCACUCUCUGGGCAGAAUCcu GAUUCUGCCCAGAGAGUGA -2.4 -2.4 -2.4 2 2 4 -40.9 65.3 9.8 5 Ib 52.6 66.8 96.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2362 NM_002559 Huesken P2RX3 5024 UCUCUGGGCAGAAUCCUUGca CAAGGAUUCUGCCCAGAGA -2.1 -2.4 -1.3 2 3 4 -40.5 62.9 -0.3 7 II 52.6 67.1 101.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2363 NM_002559 Huesken P2RX3 5024 AGAAUCCUUGCAUCUGAUUuu AAUCAGAUGCAAGGAUUCU -0.9 -2.1 1 1 0 2 -34.9 71.8 -6.3 5 II 36.8 50.1 79.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2364 NM_002559 Huesken P2RX3 5024 UCAGUAACAAUCAUCUUGGug CCAAGAUGAUUGUUACUGA -3.3 -2.4 0.6 0 4 2 -33.7 77.2 -2.6 8 Ia 36.8 75.2 98.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2365 NM_002559 Huesken P2RX3 5024 AUGACAAAGACCGAGGUGCcc GCACCUCGGUCUUUGUCAU -3.4 -1.1 0.6 2 3 3 -39.6 58.3 2.7 7 Ia 52.6 65.3 85.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2366 NM_002559 Huesken P2RX3 5024 GAGGUGCCCUGAGGUGGCGuc CGCCACCUCAGGGCACCUC -2.4 -2.4 -4.2 0 2 4 -47.5 26 0 0 II 73.7 36.1 13 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2367 NM_002559 Huesken P2RX3 5024 GGCGUCACGUAAUCAGACAca UGUCUGAUUACGUGACGCC -2.1 -3.3 -1.9 1 -3 4 -39.2 48.6 -1.5 1 III 52.6 31.5 43.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2368 NM_002559 Huesken P2RX3 5024 GUCACGUAAUCAGACACAUcc AUGUGUCUGAUUACGUGAC -1.1 -2.2 -1.9 1 -1 2 -35.5 55 -6.3 2 III 42.1 39.1 33.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2369 NM_002559 Huesken P2RX3 5024 CAUGACUCUGUUGGCGUAGag CUACGCCAACAGAGUCAUG -2.1 -2.1 1.7 -1 0 4 -38.5 54.3 3.7 5 II 52.6 46.9 53.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2370 NM_002559 Huesken P2RX3 5024 AAUGGCUGUGUCCCGUACCug GGUACGGGACACAGCCAUU -3.3 -0.9 -1.5 2 4 4 -41.9 59.9 7.5 3 Ib 57.9 66.4 61.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2371 NM_002559 Huesken P2RX3 5024 UGCAAGAAAACCCACCCUAca UAGGGUGGGUUUUCUUGCA -1.3 -2.1 -2.6 0 -1 3 -38.8 55.8 -3.4 6 II 47.4 55.6 82.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2372 NM_002559 Huesken P2RX3 5024 GAGAUGAUCAGAAGCUGAAcu UUCAGCUUCUGAUCAUCUC -0.9 -2.4 -1.2 0 -2 2 -36.5 56.4 -6.3 4 II 42.1 37.8 46.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2373 NM_002559 Huesken P2RX3 5024 CUGAACUACUCGGUUGAUGau CAUCAACCGAGUAGUUCAG -2.1 -2.1 1.1 1 0 3 -36.3 63 0.7 4 II 47.4 50.8 74.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2374 NM_002559 Huesken P2RX3 5024 CUCGGUUGAUGAUCCCGAUgg AUCGGGAUCAUCAACCGAG -1.1 -2.1 -4.7 0 -2 4 -39.4 52.9 -6 1 III 52.6 37.9 39.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2375 NM_002559 Huesken P2RX3 5024 GGUUGAUGAUCCCGAUGGUcc ACCAUCGGGAUCAUCAACC -2.2 -3.3 -0.7 0 0 4 -40.1 43.9 -6.3 3 II 52.6 25.8 25.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2376 NM_002559 Huesken P2RX3 5024 CUCUUCACAACCACCGACUug AGUCGGUGGUUGUGAAGAG -2.1 -2.1 1.3 -1 -2 3 -39.4 62.8 -13.3 5 II 52.6 51.8 64.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2377 NM_002559 Huesken P2RX3 5024 CGGUGGACUGCUUCUCCGCug GCGGAGAAGCAGUCCACCG -3.4 -2.4 -2 -1 0 4 -44.5 45.8 6.1 0 II 68.4 46.4 81.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2378 NM_002559 Huesken P2RX3 5024 GACUGCUUCUCCGCUGUGGuc CCACAGCGGAGAAGCAGUC -3.3 -2.4 -2.1 2 1 4 -43 54.6 -4.7 2 II 63.2 43.1 62.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2379 NM_002559 Huesken P2RX3 5024 GCGAUUUUCAGCGUAGUCUca AGACUACGCUGAAAAUCGC -2.1 -3.4 0.5 2 -1 3 -36.7 69.9 -4 5 II 47.4 47.4 77.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2380 NM_002559 Huesken P2RX3 5024 CAGCGUAGUCUCAUUCACCuc GGUGAAUGAGACUACGCUG -3.3 -2.1 -0.8 0 1 3 -38.8 55.3 2.8 2 II 52.6 59.3 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2381 NM_002559 Huesken P2RX3 5024 AACUUCUUGGCUUUGUACUgg AGUACAAAGCCAAGAAGUU -2.1 -0.9 1.5 3 2 3 -34.1 93.2 -1 6 II 36.8 61.5 99.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2382 NM_002559 Huesken P2RX3 5024 UUCUUGGCUUUGUACUGGUcg ACCAGUACAAAGCCAAGAA -2.2 -0.9 1.6 0 2 3 -36.5 72.9 -4 7 II 42.1 63.5 82.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2383 NM_002559 Huesken P2RX3 5024 GGCUUUGUACUGGUCGGCCcc GGCCGACCAGUACAAAGCC -3.3 -3.3 -0.9 0 2 5 -42.9 51.8 9.7 2 II 63.2 44.7 68 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2384 NM_002559 Huesken P2RX3 5024 UUGAGGAAGUUGAGCAGGAug UCCUGCUCAACUUCCUCAA -2.4 -0.9 3.6 0 1 2 -39.2 47.6 -6.3 6 II 47.4 57.5 90.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2385 NM_002559 Huesken P2RX3 5024 UCCCACAGAAGUAAAGGCCgc GGCCUUUACUUCUGUGGGA -3.3 -2.4 -1 1 3 4 -40.3 59 10.5 5 II 52.6 65.5 80.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2386 NM_002559 Huesken P2RX3 5024 CCACAGAAGUAAAGGCCGCca GCGGCCUUUACUUCUGUGG -3.4 -3.3 -0.3 0 1 6 -40.4 30.6 7.8 2 II 57.9 44.2 61.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2387 NM_002559 Huesken P2RX3 5024 GAUGAUGGUGGGGAUGAUGuu CAUCAUCCCCACCAUCAUC -2.1 -2.4 4.8 0 1 4 -39.9 48 2.7 4 II 52.6 46 38.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2388 NM_002559 Huesken P2RX3 5024 CUUCAGGAGGGUGCGGUACuc GUACCGCACCCUCCUGAAG -2.2 -2.1 1.7 1 0 4 -43.1 43.6 11.1 4 II 63.2 44.1 37.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2389 NM_002559 Huesken P2RX3 5024 GGGACACGCUGCUUUUCUCag GAGAAAAGCAGCGUGUCCC -2.4 -3.3 1.4 1 1 3 -40.6 56.1 7.4 0 II 57.9 35.4 68.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2390 NM_002559 Huesken P2RX3 5024 UCUCAGAAACGCUGUCGAGcc CUCGACAGCGUUUCUGAGA -2.1 -2.4 -1 0 3 3 -39 53 0.4 5 Ib 52.6 52.2 64.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2391 NM_002559 Huesken P2RX3 5024 CAGAAACGCUGUCGAGCCGgg CGGCUCGACAGCGUUUCUG -2.4 -2.1 -1.7 -1 1 4 -41.2 40.7 6.1 1 II 63.2 40.8 86 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2392 NM_002559 Huesken P2RX3 5024 AGAAACGCUGUCGAGCCGGgu CCGGCUCGACAGCGUUUCU -3.3 -2.1 -1.7 1 4 5 -42.4 39.3 0.4 4 Ib 63.2 58.2 98 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2393 NM_002559 Huesken P2RX3 5024 AGGAGUAUUUGGGGAUGCAcu UGCAUCCCCAAAUACUCCU -2.1 -2.1 2.3 0 0 4 -39.4 49.5 -3.8 4 II 47.4 41.7 56.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2394 NM_002559 Huesken P2RX3 5024 AAGUCGCACACCCAGCCGAuc UCGGCUGGGUGUGCGACUU -2.4 -0.9 -1.2 2 1 4 -44.3 46.1 -6.1 3 II 63.2 47.4 77.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2395 NM_002559 Huesken P2RX3 5024 CACACCCAGCCGAUCUUAAug UUAAGAUCGGCUGGGUGUG -0.9 -2.1 0.5 0 -3 4 -39.6 53.7 -8.4 3 III 52.6 29.6 55.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2396 NM_002559 Huesken P2RX3 5024 CCAGCCGAUCUUAAUGCCCag GGGCAUUAAGAUCGGCUGG -3.3 -3.3 -1 -1 1 4 -40.9 45.6 5.8 0 II 57.9 51.5 59.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2397 NM_002559 Huesken P2RX3 5024 UGCGCGCCAGUUUGGCAAAau UUUGCCAAACUGGCGCGCA -0.9 -2.1 -4.5 -1 -2 7 -41.3 46.4 -0.7 1 II 57.9 37 37.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2398 NM_002559 Huesken P2RX3 5024 UGGCAAAAUCCUGCCCCGCaa GCGGGGCAGGAUUUUGCCA -3.4 -2.1 -5.5 1 3 7 -43.7 44.3 10.8 3 Ib 63.2 60.8 67.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2399 NM_002559 Huesken P2RX3 5024 GCAAAAUCCUGCCCCGCAAac UUGCGGGGCAGGAUUUUGC -0.9 -3.4 -3 2 -2 7 -41.3 42.6 -1 2 II 57.9 27.7 33.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2400 NM_002559 Huesken P2RX3 5024 GACCACGUCCCCUACCCGCaa GCGGGUAGGGGACGUGGUC -3.4 -2.4 -1.1 2 2 5 -47.1 38.5 5.4 1 II 73.7 45.8 37.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2401 NM_002559 Huesken P2RX3 5024 ACGUCCCCUACCCGCAAGAug UCUUGCGGGUAGGGGACGU -2.4 -2.2 -1.4 0 -1 5 -44.6 43.4 -6.1 2 II 63.2 36.9 75.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2402 NM_002559 Huesken P2RX3 5024 CCGCAAGAUGGGGCAGAAAgg UUUCUGCCCCAUCUUGCGG -0.9 -3.3 -2.2 0 -5 5 -41.5 24.2 -3.1 0 III 57.9 20.4 35.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2403 NM_002559 Huesken P2RX3 5024 GGUGGAAGCGGCAGGUCUUca AAGACCUGCCGCUUCCACC -0.9 -3.3 1.7 0 -1 5 -43.9 29 -8.9 1 III 63.2 28.3 39.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2404 NM_002559 Huesken P2RX3 5024 UCUUCAUGUCCCUGGCUGUca ACAGCCAGGGACAUGAAGA -2.2 -2.4 0.8 0 1 3 -41.6 64.1 -8.7 7 II 52.6 51.9 78.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2405 NM_002559 Huesken P2RX3 5024 UUCAUGUCCCUGGCUGUCAgg UGACAGCCAGGGACAUGAA -2.1 -0.9 0.8 2 0 3 -41.6 66 -3.8 8 II 52.6 63.1 90.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2406 NM_002559 Huesken P2RX3 5024 CAUGUCCCUGGCUGUCAGGuu CCUGACAGCCAGGGACAUG -3.3 -2.1 -4.7 -2 1 3 -43.7 50 -4.4 1 II 63.2 44 33.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2407 NM_002559 Huesken P2RX3 5024 UGGCUGUCAGGUUGGGAAGga CUUCCCAACCUGACAGCCA -2.1 -2.1 2.4 1 1 3 -42.3 59.7 3 4 II 57.9 54.1 66.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2408 NM_002559 Huesken P2RX3 5024 UUCUUGAUGAAAAUAGUGAag UCACUAUUUUCAUCAAGAA -2.4 -0.9 1.1 1 1 1 -30.3 89.4 -1.7 9 II 26.3 68.9 79.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2409 NM_002559 Huesken P2RX3 5024 UAGUGAAGUUCUCAGCUUCca GAAGCUGAGAACUUCACUA -2.4 -1.3 -2.3 0 2 2 -36.1 73.5 10.5 6 Ia 42.1 68.1 88.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2410 NM_002559 Huesken P2RX3 5024 CCAUCAUGAUGGGCGUUUCca GAAACGCCCAUCAUGAUGG -2.4 -3.3 -2.4 0 -1 5 -38.6 57.2 5.4 3 II 52.6 41 48.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2411 NM_002559 Huesken P2RX3 5024 AGCCCUGGAUCUCACAGGUcc ACCUGUGAGAUCCAGGGCU -2.2 -2.1 -4.4 2 1 4 -44 49.1 -0.9 1 II 57.9 42.5 50.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2412 NM_002559 Huesken P2RX3 5024 ACAGGUCCGGAGCACAGAGcu CUCUGUGCUCCGGACCUGU -2.1 -2.2 -1.4 2 3 4 -44.2 38.8 4.7 1 II 63.2 47.8 41.9 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2413 NM_002559 Huesken P2RX3 5024 GUCCGGAGCACAGAGCUGUag ACAGCUCUGUGCUCCGGAC -2.2 -2.2 -1.8 2 -1 4 -44.3 33.2 -6.3 2 III 63.2 40.7 59.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2414 NM_002559 Huesken P2RX3 5024 CACAGAGCUGUAGUUCACGca CGUGAACUACAGCUCUGUG -2.4 -2.1 -0.5 -1 1 2 -38.4 49.1 0.3 3 II 52.6 52.5 42 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2415 NM_002559 Huesken P2RX3 5024 UGUAGUUCACGCAGCGGCCag GGCCGCUGCGUGAACUACA -3.3 -2.1 -0.3 0 4 6 -43.3 56.8 2.5 5 Ia 63.2 65.7 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2416 NM_002559 Huesken P2RX3 5024 ACGCAGCGGCCAGUGAGGAuc UCCUCACUGGCCGCUGCGU -2.4 -2.2 -0.3 3 1 6 -46.7 21 -1.1 2 II 68.4 32.4 16.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2417 NM_002559 Huesken P2RX3 5024 CCUUGCAUCUGAUUUUCAGua CUGAAAAUCAGAUGCAAGG -2.1 -3.3 -1.8 0 1 2 -34.4 73.9 0.3 2 II 42.1 43.1 85.5 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2418 NM_002559 Huesken P2RX3 5024 AUCUGAUUUUCAGUAACAAuc UUGUUACUGAAAAUCAGAU -0.9 -1.1 -2.3 2 1 1 -30.1 73.2 -3.8 4 II 26.3 47.9 54.1 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2419 NM_002559 Huesken P2RX3 5024 UCUGAUUUUCAGUAACAAUca AUUGUUACUGAAAAUCAGA -1.1 -2.4 -2.3 1 0 1 -30.1 84.3 1 5 II 26.3 60.2 74.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2420 NM_002559 Huesken P2RX3 5024 UGAUGAUGACAAAGACCGAgg UCGGUCUUUGUCAUCAUCA -2.4 -2.1 0.9 0 1 3 -36.6 52.8 -4 6 II 42.1 50.9 72.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2421 NM_002559 Huesken P2RX3 5024 CCGAGGUGCCCUGAGGUGGcg CCACCUCAGGGCACCUCGG -3.3 -3.3 -0.7 1 -1 4 -47.4 33 -1.3 2 II 73.7 41.9 70.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2422 NM_002559 Huesken P2RX3 5024 AGGUGCCCUGAGGUGGCGUca ACGCCACCUCAGGGCACCU -2.2 -2.1 -4.2 1 2 4 -47.3 40.5 0.7 1 II 68.4 39.8 8.6 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2423 NM_002559 Huesken P2RX3 5024 GGUGGCGUCACGUAAUCAGac CUGAUUACGUGACGCCACC -2.1 -3.3 -1.3 1 1 4 -40.1 48.4 -2.4 1 II 57.9 39.1 50 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2424 NM_002559 Huesken P2RX3 5024 UCCAUGACUCUGUUGGCGUag ACGCCAACAGAGUCAUGGA -2.2 -2.4 -0.6 0 2 4 -40.8 64.2 -1.6 6 II 52.6 59.1 89.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2425 NM_002559 Huesken P2RX3 5024 UUGGCGUAGAGUCCGGAGCcc GCUCCGGACUCUACGCCAA -3.4 -0.9 -1 2 3 4 -43.7 63.8 12.8 4 II 63.2 70.9 87.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2426 NM_002559 Huesken P2RX3 5024 GAGCCCUUCACCUUGGUUAcc UAACCAAGGUGAAGGGCUC -1.3 -2.4 -1 3 -2 4 -40.3 67.7 -6.1 3 III 52.6 40.5 16.2 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2427 NM_002559 Huesken P2RX3 5024 AAAACCCACCCUACAAAGUag ACUUUGUAGGGUGGGUUUU -2.2 -0.9 0 2 2 3 -36.2 67.4 -5.9 5 II 42.1 55.4 89.4 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2428 NM_002559 Huesken P2RX3 5024 GAUGAUCAGAAGCUGAACUac AGUUCAGCUUCUGAUCAUC -2.1 -2.4 -1.2 1 1 2 -36.3 67.9 5.8 3 II 42.1 48.1 72.3 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2429 NM_002559 Huesken P2RX3 5024 AUCAGAAGCUGAACUACUCgg GAGUAGUUCAGCUUCUGAU -2.4 -1.1 -1.2 2 3 2 -36.3 63.8 4.8 4 Ia 42.1 62.3 91.8 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2430 NM_002559 Huesken P2RX3 5024 GAAGCUGAACUACUCGGUUga AACCGAGUAGUUCAGCUUC -0.9 -2.4 -0.9 0 1 3 -37.4 53.6 0.8 3 III 47.4 43 62 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2431 NM_002559 Huesken P2RX3 5024 GAUGAUCCCGAUGGUCCAGcu CUGGACCAUCGGGAUCAUC -2.1 -2.4 -0.7 0 2 4 -41.5 47.4 8 2 II 57.9 38.3 60.7 Luciferase reporter assay HeLa 50nM 48h "Design of a genome-wide siRNA library using an artificial neural network" 16025102 2005 The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test set (Pearson coefficient r = 0.66) and siRNAs targeting endogenous genes at mRNA and protein levels. Neural networks trained on a complementary 21-nucleotide (nt) guide sequence were superior to those trained on a 19-nt sequence. BIOPREDsi was used in the design of a genome-wide siRNA collection with two potent siRNAs per gene. When this collection of 50,000 siRNAs was used to identify genes involved in the cellular response to hypoxia, two of the most potent hits were the key hypoxia transcription factors HIF1A and ARNT. Nature biotechnology 2005/8/1 Si2432 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2433 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2434 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2435 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2436 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2437 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2438 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2439 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2440 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2441 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2442 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2443 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2444 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2445 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2446 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2447 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2448 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2449 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2450 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2451 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2452 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2453 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2454 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2455 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2456 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2457 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2458 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2459 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2460 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2461 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2462 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2463 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2464 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2465 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2466 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2467 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2468 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2469 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2470 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2471 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2472 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2473 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2474 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2475 AH001498 Harborth Lamin A 33782 GAGCUCCUGCAGGUCCUCCuu GGAGGACCUGCAGGAGCUC -3.3 -2.4 -1 2 2 2 -46.5 48 12 1 II 68.4 46 83 Western blotting HeLa 100nM 24h Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. 12804036 2003 Small interfering RNAs (siRNAs) induce sequence-specific gene silencing in mammalian cells and guide mRNA degradation in the process of RNA interference (RNAi). By targeting endogenous lamin A/C mRNA in human HeLa or mouse SW3T3 cells, we investigated the positional variation of siRNA-mediated gene silencing. We find cell-type-dependent global effects and cell-type-independent positional effects. HeLa cells were about 2-fold more responsive to siRNAs than SW3T3 cells but displayed a very similar pattern of positional variation of lamin A/C silencing. In HeLa cells, 26 of 44 tested standard 21-nucleotide (nt) siRNA duplexes reduced the protein expression by at least 90%, and only 2 duplexes reduced the lamin A/C proteins to <50%. Fluorescent chromophores did not perturb gene silencing when conjugated to the 5'-end or 3'-end of the sense siRNA strand and the 5'-end of the antisense siRNA strand, but conjugation to the 3'-end of the antisense siRNA abolished gene silencing. RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorothioate. Synthetic RNA hairpin loops were subsequently evaluated for lamin A/C silencing as a function of stem length and loop composition. As long as the 5'-end of the guide strand coincided with the 5'-end of the hairpin RNA, 19-29 base pair (bp) hairpins effectively silenced lamin A/C, but when the hairpin started with the 5'-end of the sense strand, only 21-29 bp hairpins were highly active. Antisense & Nucleic Acid Drug Development 2003/4/1 Si2476 M15077 Ui-Tei FireflyLuc 116160065 UCUUUAUGUUUUUGGCGUCuu GACGCCAAAAACAUAAAGA -2.4 -2.4 0 3 4 -32.4 80.6 10.4 7 Ia 36.8 62.9 85.8 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2477 M15077 Ui-Tei FireflyLuc 116160065 UUCUUUAUGUUUUUGGCGUcu ACGCCAAAAACAUAAAGAA -2.2 -0.9 1 3 4 -30.9 97.4 1.4 7 II 31.6 70.3 94.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2478 M15077 Ui-Tei FireflyLuc 116160065 GGGCCUUUCUUUAUGUUUUug AAAACAUAAAGAAAGGCCC -0.9 -3.3 3 -2 5 -32.9 77.2 -1.2 2 III 36.8 41.3 11.1 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2479 M15077 Ui-Tei FireflyLuc 116160065 CCGGGCCUUUCUUUAUGUUuu AACAUAAAGAAAGGCCCGG -0.9 -3.3 -1 -2 7 -36.8 55.4 -3 0 III 47.4 29.8 7.6 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2480 M15077 Ui-Tei FireflyLuc 116160065 GGCGCCGGGCCUUUCUUUAug UAAAGAAAGGCCCGGCGCC -1.3 -3.3 -2.2 1 -3 11 -43 46.4 -0.8 0 III 63.2 23.8 5.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2481 M15077 Ui-Tei FireflyLuc 116160065 UAGAAUGGCGCCGGGCCUUuc AAGGCCCGGCGCCAUUCUA -0.9 -1.3 -3.9 0 1 11 -44.4 41.4 -6 5 II 63.2 55.6 23 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2482 M15077 Ui-Tei FireflyLuc 116160065 AGCGGAUAGAAUGGCGCCGgg CGGCGCCAUUCUAUCCGCU -2.4 -2.1 -1.9 2 3 7 -42.8 41.2 5.3 2 II 63.2 52.3 53.8 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2483 M15077 Ui-Tei FireflyLuc 116160065 UCUUCCAGCGGAUAGAAUGgc CAUUCUAUCCGCUGGAAGA -2.1 -2.4 -1.7 1 2 4 -37.8 73.2 0 5 Ib 47.4 64.9 93.2 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2484 M15077 Ui-Tei FireflyLuc 116160065 GUUCCAUCUUCCAGCGGAUag AUCCGCUGGAAGAUGGAAC -1.1 -2.2 -2.2 1 0 4 -39.9 46.4 -11.3 2 II 52.6 32.1 23.4 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2485 M15077 Ui-Tei FireflyLuc 116160065 CCAGCGGUUCCAUCUUCCAgc UGGAAGAUGGAACCGCUGG -2.1 -3.3 0.3 -1 -2 4 -41.8 42.4 -8.1 1 III 57.9 36.8 16.6 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2486 M15077 Ui-Tei FireflyLuc 116160065 UGCUCUCCAGCGGUUCCAUcu AUGGAACCGCUGGAGAGCA -1.1 -2.1 -2.6 0 1 4 -43.1 57.6 -4 2 II 57.9 43.6 35.4 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2487 M15077 Ui-Tei FireflyLuc 116160065 UUUCAUAGCUUCUGCCAACcg GUUGGCAGAAGCUAUGAAA -2.2 -0.9 -2.7 1 3 3 -35.7 71.7 7.8 6 Ia 42.1 69.1 93.1 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2488 M15077 Ui-Tei FireflyLuc 116160065 CGCGCCCAACACCGGCAUAaa UAUGCCGGUGUUGGGCGCG -1.3 -2.4 -4.1 -2 -5 7 -44.6 28.3 -3.4 -2 III 68.4 17.1 19.7 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2489 M15077 Ui-Tei FireflyLuc 116160065 UAAAUAACGCGCCCAACACcg GUGUUGGGCGCGUUAUUUA -2.2 -1.3 -2.2 1 4 7 -36.3 69.2 7.5 7 Ia 47.4 69.4 91.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2490 M15077 Ui-Tei FireflyLuc 116160065 CGCGGGCGCAACUGCAACUcc AGUUGCAGUUGCGCCCGCG -2.1 -2.4 -1.5 -1 -3 9 -44.1 32.4 -6 -1 III 68.4 33.9 37.3 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2491 M15077 Ui-Tei FireflyLuc 116160065 UUAUAAAUGUCGUUCGCGGgc CCGCGAACGACAUUUAUAA -3.3 -0.9 0.7 1 6 5 -33.6 78.2 2.7 8 Ia 42.1 73.9 94.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2492 M15077 Ui-Tei FireflyLuc 116160065 GGGAGCUUUUUUUGCACGUuc ACGUGCAAAAAAAGCUCCC -2.2 -3.3 -0.2 0 -1 3 -36.4 58.9 -1 2 III 47.4 38 30 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2493 M15077 Ui-Tei FireflyLuc 116160065 UAAUUUUUUGGAUGAUUGGga CCAAUCAUCCAAAAAAUUA -3.3 -1.3 3.8 0 4 2 -28.6 98.5 0 9 Ia 26.3 77.9 97.5 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2494 M15077 Ui-Tei FireflyLuc 116160065 AUUCAUUAAAACCGGGAGGua CCUCCCGGUUUUAAUGAAU -3.3 -1.1 0.3 2 4 5 -34.8 72.9 5.1 7 Ia 42.1 65.6 73.5 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2495 M15077 Ui-Tei FireflyLuc 116160065 UUCUAUGAGGCAGAGCGACac GUCGCUCUGCCUCAUAGAA -2.2 -0.9 -0.4 1 3 3 -40.2 54.8 7.8 7 Ia 52.6 63.4 69.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2496 M15077 Ui-Tei FireflyLuc 116160065 AAUAGGAUCUCUGGCAUGCga GCAUGCCAGAGAUCCUAUU -3.4 -0.9 1.5 1 4 3 -38.7 65.5 8.1 7 Ia 47.4 63.8 94.5 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2497 M15077 Ui-Tei FireflyLuc 116160065 UUAAAAUCGCAGUAUCCGGaa CCGGAUACUGCGAUUUUAA -3.3 -0.9 0.7 2 5 4 -34.4 76.1 5 8 Ia 42.1 76.1 96.3 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2498 M15077 Ui-Tei FireflyLuc 116160065 UAGUAAACAUUCCAAAACCgu GGUUUUGGAAUGUUUACUA -3.3 -1.3 1.4 0 3 2 -31 79 10.2 7 Ia 31.6 76.7 93.3 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2499 M15077 Ui-Tei FireflyLuc 116160065 AUUAAGACGACUCGAAAUCca GAUUUCGAGUCGUCUUAAU -2.4 -1.1 -0.5 1 3 2 -32.5 72.9 13.2 8 Ia 36.8 66.9 98.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2500 M15077 Ui-Tei FireflyLuc 116160065 AAUCUUGUAAUCCUGAAGGcu CCUUCAGGAUUACAAGAUU -3.3 -0.9 -0.5 2 5 2 -33.6 85.2 2.4 7 Ia 36.8 72 98.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2501 M15077 Ui-Tei FireflyLuc 116160065 UAGAUAAAUCGUAUUUGUCaa GACAAAUACGAUUUAUCUA -2.4 -1.3 1.4 0 4 2 -29 94 10.2 7 Ia 26.3 74.8 86.5 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2502 M15077 Ui-Tei FireflyLuc 116160065 AUUAGAUAAAUCGUAUUUGuc CAAAUACGAUUUAUCUAAU -2.1 -1.1 1.4 2 4 2 -26.4 89.6 0 8 Ia 21.1 70.7 87.8 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2503 M15077 Ui-Tei FireflyLuc 116160065 CCCUCGGGUGUAAUCAGAAua UUCUGAUUACACCCGAGGG -0.9 -3.3 -1.1 -1 -3 4 -39.8 41.3 -6 1 III 52.6 29.8 10.7 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2504 M15077 Ui-Tei FireflyLuc 116160065 CCGCGCCCGGUUUAUCAUCcc GAUGAUAAACCGGGCGCGG -2.4 -3.3 -2 1 -2 10 -41.6 40 8.4 -2 II 63.2 38.8 52.9 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2505 M15077 Ui-Tei FireflyLuc 116160065 AACUUUACCGACCGCGCCCgg GGGCGCGGUCGGUAAAGUU -3.3 -0.9 -1.3 1 4 8 -42.3 60.8 9.8 4 Ia 63.2 64.9 93.6 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2506 M15077 Ui-Tei FireflyLuc 116160065 AAAAUGGAACAACUUUACCga GGUAAAGUUGUUCCAUUUU -3.3 -0.9 0 1 5 2 -30.6 83.6 14.4 7 Ia 31.6 72.3 94.5 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2507 M15077 Ui-Tei FireflyLuc 116160065 UACAUAACCGGACAUAAUCau GAUUAUGUCCGGUUAUGUA -2.4 -1.3 0.9 1 2 4 -33.6 80.3 9.8 7 Ia 36.8 73.5 96.8 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2508 M15077 Ui-Tei FireflyLuc 116160065 AGAAUGUAGCCAUCCAUCCuu GGAUGGAUGGCUACAUUCU -3.3 -2.1 -4 3 3 3 -38.7 69.2 5.1 6 Ia 47.4 68.9 97.4 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2509 M15077 Ui-Tei FireflyLuc 116160065 UUAAUCAGAGACUUCAGGCgg GCCUGAAGUCUCUGAUUAA -3.4 -0.9 0.8 0 6 3 -36.2 86.6 9.7 8 Ia 42.1 81.5 95.6 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2510 M15077 Ui-Tei FireflyLuc 116160065 CGGCGGCGGGAAGUUCACCgg GGUGAACUUCCCGCCGCCG -3.3 -2.4 -4.5 1 0 10 -45.7 24.8 10 -2 II 73.7 39.1 14.5 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2511 M15077 Ui-Tei FireflyLuc 116160065 AAACAACAACGGCGGCGGGaa CCCGCCGCCGUUGUUGUUU -3.3 -0.9 1.6 1 5 10 -41.6 36.2 5.1 4 Ia 63.2 46.9 42.3 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2512 M15077 Ui-Tei FireflyLuc 116160065 CAAAACAACAACGGCGGCGgg CGCCGCCGUUGUUGUUUUG -2.4 -2.1 1.9 -1 2 8 -38 48.7 0.7 5 II 57.9 56.5 51.3 Luciferase reporter assay CHO-K1;HeLa;E14TG2a ;S2 50nM 24h Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference 14769950 2004 In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi. Nucleic Acids Research 2004/3/1 Si2513 NM_001632 Khovorova SEAP 250 CAGAAGUCCGGGUUCUCCUcc AGGAGAACCCGGACUUCUG -2.1 -2.1 -2.7 1 0 5 -41.9 60.3 -0.9 2 II 57.9 51.8 81 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2514 NM_001632 Khovorova SEAP 250 CCCAGGAAGAUGAUGAGGUuc ACCUCAUCAUCUUCCUGGG -2.2 -3.3 -0.3 0 -1 3 -40.7 44.7 -6.2 3 III 52.6 42.4 49 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2515 NM_001632 Khovorova SEAP 250 ACUGUCUGGCACAUGUUUGuc CAAACAUGUGCCAGACAGU -2.1 -2.2 0 3 3 3 -37.6 70.2 -0.3 6 Ib 47.4 57.6 88 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2516 NM_001632 Khovorova SEAP 250 GGCGAGGCGUGCUGCACUCgu GAGUGCAGCACGCCUCGCC -2.4 -3.3 -0.7 0 0 4 -46.8 25.7 7.8 1 II 73.7 32.6 -5 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2517 NM_001632 Khovorova SEAP 250 CAGCCAUUCCUGCACCAGAuu UCUGGUGCAGGAAUGGCUG -2.4 -2.1 -0.4 2 -3 3 -42.5 45.9 -3.4 1 III 57.9 40.1 30 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2518 NM_001632 Khovorova SEAP 250 GAACAUGAUCGUCUCAGUCag GACUGAGACGAUCAUGUUC -2.4 -2.4 -0.2 1 3 2 -37 64 17.9 4 II 47.4 52.6 85 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2519 NM_001632 Khovorova SEAP 250 CUGGUGAGCUGGCCCGCCCuc GGGCGGGCCAGCUCACCAG -3.3 -2.1 -5.5 0 1 9 -49.6 35.3 7.8 1 II 78.9 51.9 20 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2520 NM_001632 Khovorova SEAP 250 GUGGGAGUGGUCGGCAGUGac CACUGCCGACCACUCCCAC -2.1 -2.2 1.9 0 1 4 -45.2 21.8 -2.4 1 II 68.4 39.2 -10 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2521 NM_001632 Khovorova SEAP 250 AACAUCCGGCCGGGCGCCGuc CGGCGCCCGGCCGGAUGUU -2.4 -0.9 -6.4 1 4 14 -48.3 29.8 -2.4 3 Ib 78.9 48 60 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2522 NM_001632 Khovorova SEAP 250 UCGCUCUCGGUAACAUCCGgc CGGAUGUUACCGAGAGCGA -2.4 -2.4 -2.5 3 3 3 -40.8 53 -2.6 3 II 57.9 66.9 32 Flow cytometry and immunofluorescence HEK293 0.25ug/Ml 24h Functional siRNAs and miRNAs Exhibit Strand Biasunctional siRNAs and miRNAs Exhibit Strand Bias 14567918 2003 Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5′-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Δ0.5 kcal/mol) at the 5′-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC. Cell 2003/10/17 Si2523 M15077 Reynolds Firefly luciferase 116160065 CUUGACUGGCGACGUAAUCca GAUUACGUCGCCAGUCAAG -2.4 -2.1 -0.8 0 0 4 -37.9 53 10.5 4 II 52.6 48.1 96 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2524 M15077 Reynolds Firefly luciferase 116160065 UGCGUCGAGUUUUCCGGUAag UACCGGAAAACUCGACGCA -1.3 -2.1 -0.2 1 -1 4 -39.2 56.2 -0.7 5 II 52.6 46.6 95.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2525 M15077 Reynolds Firefly luciferase 116160065 UCUGAUUUUUCUUGCGUCGag CGACGCAAGAAAAAUCAGA -2.4 -2.4 1 0 3 3 -34 80.5 3.4 7 Ia 42.1 68.9 95.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2526 M15077 Reynolds Firefly luciferase 116160065 AACUCCUCCGCGCAACUUUuu AAAGUUGCGCGGAGGAGUU -0.9 -0.9 0.8 3 0 6 -39.4 64.7 -3.9 6 II 52.6 51.5 95.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2527 M15077 Reynolds Firefly luciferase 116160065 UCGUCCACAAACACAACUCcu GAGUUGUGUUUGUGGACGA -2.4 -2.4 -0.4 0 2 2 -37.1 72.1 4.8 6 II 47.4 68 95.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2528 M15077 Reynolds Firefly luciferase 116160065 UCUCUCUGAUUUUUCUUGCgu GCAAGAAAAAUCAGAGAGA -3.4 -2.4 1 2 4 2 -33.6 93 12.8 7 Ib 36.8 70.3 95.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2529 M15077 Reynolds Firefly luciferase 116160065 UUUCCGGUAAGACCUUUCGgu CGAAAGGUCUUACCGGAAA -2.4 -0.9 -1.5 1 4 4 -36.3 78.8 2.4 7 II 47.4 73.9 95 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2530 M15077 Reynolds Firefly luciferase 116160065 CUUGCGUCGAGUUUUCCGGua CCGGAAAACUCGACGCAAG -3.3 -2.1 -0.2 1 3 4 -38.7 69.5 3.4 3 II 57.9 57.7 94.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2531 M15077 Reynolds Firefly luciferase 116160065 UCCGGUAAGACCUUUCGGUac ACCGAAAGGUCUUACCGGA -2.2 -2.4 -4.7 1 2 4 -40 60.3 -6.3 4 II 52.6 57.7 94.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2532 M15077 Reynolds Firefly luciferase 116160065 UUUUCUUGCGUCGAGUUUUcc AAAACUCGACGCAAGAAAA -0.9 -0.9 0.9 2 1 3 -32.4 84.8 -6.3 8 II 36.8 69.1 94.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2533 M15077 Reynolds Firefly luciferase 116160065 CGUCGAGUUUUCCGGUAAGac CUUACCGGAAAACUCGACG -2.1 -2.4 -0.2 -1 -1 4 -36.7 42.7 -2 2 II 52.6 32.8 94.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2534 M15077 Reynolds Firefly luciferase 116160065 UGACUGGCGACGUAAUCCAcg UGGAUUACGUCGCCAGUCA -2.1 -2.1 -0.8 2 1 4 -40.3 53.2 -6.1 7 II 52.6 58.2 93.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2535 M15077 Reynolds Firefly luciferase 116160065 ACAACUCCUCCGCGCAACUuu AGUUGCGCGGAGGAGUUGU -2.1 -2.2 0.8 0 1 6 -41.9 48.5 -3.9 3 II 57.9 46.7 93.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2536 M15077 Reynolds Firefly luciferase 116160065 CCACAAACACAACUCCUCCgc GGAGGAGUUGUGUUUGUGG -3.3 -3.3 2.7 0 1 2 -38.8 53.3 15.1 4 II 52.6 52.2 93.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2537 M15077 Reynolds Firefly luciferase 116160065 UCUUUUUCCGUCAUCGUCUuu AGACGAUGACGGAAAAAGA -2.1 -2.4 0.3 2 2 3 -35.5 85.2 -6.6 8 II 42.1 71.7 93.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2538 M15077 Reynolds Firefly luciferase 116160065 AAGACCUUUCGGUACUUCGuc CGAAGUACCGAAAGGUCUU -2.4 -0.9 -4.9 2 3 3 -36.4 81.6 0 5 Ib 47.4 68.3 93.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2539 M15077 Reynolds Firefly luciferase 116160065 UACUUGACUGGCGACGUAAuc UUACGUCGCCAGUCAAGUA -0.9 -1.3 1.3 0 -1 4 -37.9 64 -6.1 8 II 47.4 55.1 92.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2540 M15077 Reynolds Firefly luciferase 116160065 UUCUUGCGUCGAGUUUUCCgg GGAAAACUCGACGCAAGAA -3.3 -0.9 0.9 0 4 3 -36.3 75.9 9.7 7 Ib 47.4 68.6 92.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2541 M15077 Reynolds Firefly luciferase 116160065 CCUUUAUGAGGAUCUCUCUga AGAGAGAUCCUCAUAAAGG -2.1 -3.3 -2.3 0 -2 2 -36.5 70.9 -6 4 II 42.1 44.3 92.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2542 M15077 Reynolds Firefly luciferase 116160065 ACAAACACAACUCCUCCGCgc GCGGAGGAGUUGUGUUUGU -3.4 -2.2 0.7 1 4 4 -39.2 64.1 13.2 7 Ia 52.6 62.8 92.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2543 M15077 Reynolds Firefly luciferase 116160065 UAUGAGGAUCUCUCUGAUUuu AAUCAGAGAGAUCCUCAUA -0.9 -1.3 -2.3 0 1 2 -35.8 70.2 -3.6 6 II 36.8 63.7 91.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2544 M15077 Reynolds Firefly luciferase 116160065 AUCCACGAUCUCUUUUUCCgu GGAAAAAGAGAUCGUGGAU -3.3 -1.1 1.2 2 4 2 -35.3 76.3 10.1 6 II 42.1 66.9 91.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2545 M15077 Reynolds Firefly luciferase 116160065 UAAUCCACGAUCUCUUUUUcc AAAAAGAGAUCGUGGAUUA -0.9 -1.3 0.4 1 1 2 -31.8 93.1 -6.3 9 II 31.6 70.2 91.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2546 M15077 Reynolds Firefly luciferase 116160065 UACUUCGUCCACAAACACAac UGUGUUUGUGGACGAAGUA -2.1 -1.3 -0.4 1 0 2 -36 72.9 -6.4 7 II 42.1 62.9 90.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2547 M15077 Reynolds Firefly luciferase 116160065 AUUUUUCUUGCGUCGAGUUuu AACUCGACGCAAGAAAAAU -0.9 -1.1 0.9 1 2 3 -32.6 83.1 -6.3 6 II 36.8 57.1 90.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2548 M15077 Reynolds Firefly luciferase 116160065 CUUCGUCCACAAACACAACuc GUUGUGUUUGUGGACGAAG -2.2 -2.1 -0.5 0 0 2 -35.6 55.5 5.1 2 II 47.4 46.6 90.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2549 M15077 Reynolds Firefly luciferase 116160065 GAGUUUUCCGGUAAGACCUuu AGGUCUUACCGGAAAACUC -2.1 -2.4 -1.5 2 0 4 -37.3 71.5 -3.5 3 II 47.4 54 90.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2550 M15077 Reynolds Firefly luciferase 116160065 GACCUUUCGGUACUUCGUCca GACGAAGUACCGAAAGGUC -2.4 -2.4 -4.9 3 2 3 -38 61.1 12.1 2 II 52.6 50.8 89.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2551 M15077 Reynolds Firefly luciferase 116160065 UGCUCCAAAACAACAACGGcg CCGUUGUUGUUUUGGAGCA -3.3 -2.1 -0.5 0 3 3 -36.4 67 -4.9 6 II 47.4 65.8 89.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2552 M15077 Reynolds Firefly luciferase 116160065 UUUCCGUGCUCCAAAACAAca UUGUUUUGGAGCACGGAAA -0.9 -0.9 -1.4 3 1 3 -35.4 63.3 -11 5 II 42.1 57.5 89.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2553 M15077 Reynolds Firefly luciferase 116160065 ACGAUCUCUUUUUCCGUCAuc UGACGGAAAAAGAGAUCGU -2.1 -2.2 0.6 2 -1 3 -35.5 76 -0.7 6 II 42.1 53.7 88.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2554 M15077 Reynolds Firefly luciferase 116160065 UCGCGGUUGUUACUUGACUgg AGUCAAGUAACAACCGCGA -2.1 -2.4 1.1 3 1 5 -37.5 59.6 0.8 4 II 47.4 57.9 88.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2555 M15077 Reynolds Firefly luciferase 116160065 UUUCGCGGUUGUUACUUGAcu UCAAGUAACAACCGCGAAA -2.4 -0.9 1.2 1 1 5 -35 73.7 -0.7 7 II 42.1 58.3 88.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2556 M15077 Reynolds Firefly luciferase 116160065 UGAGGAUCUCUCUGAUUUUuc AAAAUCAGAGAGAUCCUCA -0.9 -2.1 -2.3 0 0 2 -35.2 64.8 -6.3 5 II 36.8 55.8 88.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2557 M15077 Reynolds Firefly luciferase 116160065 UUUCCGUCAUCGUCUUUCCgu GGAAAGACGAUGACGGAAA -3.3 -0.9 0.3 2 4 3 -36.7 83.5 5.1 7 Ib 47.4 73.7 87.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2558 M15077 Reynolds Firefly luciferase 116160065 UCUCUGAUUUUUCUUGCGUcg ACGCAAGAAAAAUCAGAGA -2.2 -2.4 1 1 3 3 -33.7 79.2 3.8 6 II 36.8 61.5 87.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2559 M15077 Reynolds Firefly luciferase 116160065 GUCCACAAACACAACUCCUcc AGGAGUUGUGUUUGUGGAC -2.1 -2.2 1.5 1 0 2 -37.7 53.4 -3.9 3 III 47.4 46.1 87.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2560 M15077 Reynolds Firefly luciferase 116160065 ACUGGCGACGUAAUCCACGau CGUGGAUUACGUCGCCAGU -2.4 -2.2 -1.4 2 4 4 -40.4 45.9 -0.3 2 II 57.9 60.9 87.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2561 M15077 Reynolds Firefly luciferase 116160065 AAACACAACUCCUCCGCGCaa GCGCGGAGGAGUUGUGUUU -3.4 -0.9 -2.6 3 5 6 -40.7 56 5.4 4 Ia 57.9 64.3 86.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2562 M15077 Reynolds Firefly luciferase 116160065 AGGAUCUCUCUGAUUUUUCuu GAAAAAUCAGAGAGAUCCU -2.4 -2.1 0.7 2 2 2 -34 82.7 7.1 6 Ib 36.8 63.6 86.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2563 M15077 Reynolds Firefly luciferase 116160065 ACUUUUUCGCGGUUGUUACuu GUAACAACCGCGAAAAAGU -2.2 -2.2 0.9 3 3 5 -33.6 88.8 9.7 7 Ia 42.1 57.8 85.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2564 M15077 Reynolds Firefly luciferase 116160065 GUUACUUGACUGGCGACGUaa ACGUCGCCAGUCAAGUAAC -2.2 -2.2 1.9 1 1 4 -38.8 58.8 -4 4 II 52.6 46.3 84.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2565 M15077 Reynolds Firefly luciferase 116160065 GACGUAAUCCACGAUCUCUuu AGAGAUCGUGGAUUACGUC -2.1 -2.4 -0.1 1 -1 2 -37.4 58.2 -4 4 II 47.4 45.2 82.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2566 M15077 Reynolds Firefly luciferase 116160065 UCCGUGCUCCAAAACAACAac UGUUGUUUUGGAGCACGGA -2.1 -2.4 -0.3 1 -1 3 -37.9 55.6 -4 4 II 47.4 55.2 82.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2567 M15077 Reynolds Firefly luciferase 116160065 UCUCUUUUUCCGUCAUCGUcu ACGAUGACGGAAAAAGAGA -2.2 -2.4 0.3 2 2 3 -35.5 78 -6.3 6 II 42.1 60.9 80.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2568 M15077 Reynolds Firefly luciferase 116160065 CGGUAAGACCUUUCGGUACuu GUACCGAAAGGUCUUACCG -2.2 -2.4 -4.9 0 -2 3 -37.8 57.5 11.1 3 II 52.6 41.3 80.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2569 M15077 Reynolds Firefly luciferase 116160065 GGUUGUUACUUGACUGGCGac CGCCAGUCAAGUAACAACC -2.4 -3.3 1.1 2 2 4 -38.1 58.7 -2.6 3 II 52.6 48.1 79.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2570 M15077 Reynolds Firefly luciferase 116160065 CCUCCGCGCAACUUUUUCGcg CGAAAAAGUUGCGCGGAGG -2.4 -3.3 1.5 1 1 6 -38.4 62.9 0.3 2 II 57.9 47.2 78.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2571 M15077 Reynolds Firefly luciferase 116160065 UUGGCCUUUAUGAGGAUCUcu AGAUCCUCAUAAAGGCCAA -2.1 -0.9 -0.5 0 1 4 -37.2 75.1 -6.6 7 II 42.1 71 78.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2572 M15077 Reynolds Firefly luciferase 116160065 UUUCGGUACUUCGUCCACAaa UGUGGACGAAGUACCGAAA -2.1 -0.9 -0.7 3 2 3 -37.7 62.1 -3.8 6 II 47.4 64.9 77.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2573 M15077 Reynolds Firefly luciferase 116160065 UUUUUCGCGGUUGUUACUUga AAGUAACAACCGCGAAAAA -0.9 -0.9 1.2 1 3 5 -32.3 83.6 1.4 8 II 36.8 67 76.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2574 M15077 Reynolds Firefly luciferase 116160065 CUCCAAAACAACAACGGCGgc CGCCGUUGUUGUUUUGGAG -2.4 -2.1 -0.7 1 1 5 -36.7 51.5 -1.9 4 II 52.6 57.9 74.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2575 M15077 Reynolds Firefly luciferase 116160065 UUUUUCCGUCAUCGUCUUUcc AAAGACGAUGACGGAAAAA -0.9 -0.9 0.3 -1 1 3 -32.8 84.4 3.8 8 II 36.8 57.1 73.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2576 M15077 Reynolds Firefly luciferase 116160065 UCCGUCAUCGUCUUUCCGUgc ACGGAAAGACGAUGACGGA -2.2 -2.4 -1 1 2 3 -39.5 66.9 -4 4 II 52.6 60.2 73.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2577 M15077 Reynolds Firefly luciferase 116160065 GUUUUCCGGUAAGACCUUUcg AAAGGUCUUACCGGAAAAC -0.9 -2.2 -1.5 1 -1 4 -34.6 61 -1.7 4 II 42.1 38.7 71.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2578 M15077 Reynolds Firefly luciferase 116160065 CCUUUCGGUACUUCGUCCAca UGGACGAAGUACCGAAAGG -2.1 -3.3 -3.4 -1 -2 3 -38.8 63.7 -5.1 4 III 52.6 40.3 70.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2579 M15077 Reynolds Firefly luciferase 116160065 GAUCUCUCUGAUUUUUCUUgc AAGAAAAAUCAGAGAGAUC -0.9 -2.4 0.7 2 1 1 -31.6 90.6 3.7 4 II 31.6 48.7 68.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2580 M15077 Reynolds Firefly luciferase 116160065 GCGACGUAAUCCACGAUCUcu AGAUCGUGGAUUACGUCGC -2.1 -3.4 -0.6 1 -2 3 -38.7 52.3 -11.3 3 III 52.6 39.9 67 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2581 M15077 Reynolds Firefly luciferase 116160065 GCGGUUGUUACUUGACUGGcg CCAGUCAAGUAACAACCGC -3.3 -3.4 1.1 -1 0 4 -38.1 56.9 0.7 4 II 52.6 44.4 66.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2582 M15077 Reynolds Firefly luciferase 116160065 GUAAGACCUUUCGGUACUUcg AAGUACCGAAAGGUCUUAC -0.9 -2.2 -4.9 -1 0 3 -35.1 46.1 -6.3 2 II 42.1 36.3 64.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2583 M15077 Reynolds Firefly luciferase 116160065 AACGGCGGCGGGAAGUUCAcc UGAACUUCCCGCCGCCGUU -2.1 -0.9 1.6 2 0 10 -43.3 41.3 -6.3 4 II 63.2 47.5 63.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2584 M15077 Reynolds Firefly luciferase 116160065 UCGAGUUUUCCGGUAAGACcu GUCUUACCGGAAAACUCGA -2.2 -2.4 -0.2 1 3 4 -36.7 67 7.4 5 Ib 47.4 62.1 61 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2585 M15077 Reynolds Firefly luciferase 116160065 CCACGAUCUCUUUUUCCGUca ACGGAAAAAGAGAUCGUGG -2.2 -3.3 0.3 1 0 3 -36.4 57.8 -0.6 2 III 47.4 42.8 58.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2586 M15077 Reynolds Firefly luciferase 116160065 AUCGUCUUUCCGUGCUCCAaa UGGAGCACGGAAAGACGAU -2.1 -1.1 -1 1 1 3 -40.1 61.1 -6.1 4 II 52.6 51.3 52.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2587 M15077 Reynolds Firefly luciferase 116160065 GAUCUCUUUUUCCGUCAUCgu GAUGACGGAAAAAGAGAUC -2.4 -2.4 2.6 1 1 3 -34.4 69 7.5 4 II 42.1 49 47.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2588 M15077 Reynolds Firefly luciferase 116160065 CGUAAUCCACGAUCUCUUUuu AAAGAGAUCGUGGAUUACG -0.9 -2.4 0.4 -1 -3 2 -34.6 67 -3.3 4 II 42.1 37.6 47.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2589 M15077 Reynolds Firefly luciferase 116160065 CAACAACGGCGGCGGGAAGuu CUUCCCGCCGCCGUUGUUG -2.1 -2.1 1.6 0 0 10 -43 26.4 3.1 2 II 68.4 30.6 47.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2590 M15077 Reynolds Firefly luciferase 116160065 UUGUUACUUGACUGGCGACgu GUCGCCAGUCAAGUAACAA -2.2 -0.9 1.1 -1 3 4 -37.2 71.3 7.4 6 Ia 47.4 60.7 44.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2591 M15077 Reynolds Firefly luciferase 116160065 UGGCGACGUAAUCCACGAUcu AUCGUGGAUUACGUCGCCA -1.1 -2.1 -1.4 1 0 4 -39.6 51 3.8 3 II 52.6 43.8 44.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2592 M15077 Reynolds Firefly luciferase 116160065 AACAACAACGGCGGCGGGAag UCCCGCCGCCGUUGUUGUU -2.4 -0.9 1.6 1 1 10 -43.1 37.8 -3.4 5 II 63.2 43 43.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2593 M15077 Reynolds Firefly luciferase 116160065 CGUCAUCGUCUUUCCGUGCuc GCACGGAAAGACGAUGACG -3.4 -2.4 -1 0 0 3 -39.3 56.5 11.1 1 II 57.9 46.1 39.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2594 M15077 Reynolds Firefly luciferase 116160065 CUCCUCCGCGCAACUUUUUcg AAAAAGUUGCGCGGAGGAG -0.9 -2.1 1.5 1 -3 6 -38.1 51.7 -10.9 3 III 52.6 37.8 38.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2595 M15077 Reynolds Firefly luciferase 116160065 GGCCUUUAUGAGGAUCUCUcu AGAGAUCCUCAUAAAGGCC -2.1 -3.3 -0.7 2 -2 4 -38.7 58.1 -1.7 3 III 47.4 41.3 38.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2596 M15077 Reynolds Firefly luciferase 116160065 GGUACUUCGUCCACAAACAca UGUUUGUGGACGAAGUACC -2.1 -3.3 -0.4 2 -2 2 -37.2 59.2 -11 3 II 47.4 39.3 35.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2597 M15077 Reynolds Firefly luciferase 116160065 CGUGCUCCAAAACAACAACgg GUUGUUGUUUUGGAGCACG -2.2 -2.4 -0.3 -1 -1 2 -35.3 59.1 10.1 2 II 47.4 43.5 32.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2598 M15077 Reynolds Firefly luciferase 116160065 UCCGCGCAACUUUUUCGCGgu CGCGAAAAAGUUGCGCGGA -2.4 -2.4 -4.4 0 4 6 -38.8 60.2 5.4 1 II 57.9 58.4 32.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2599 M15077 Reynolds Firefly luciferase 116160065 CGCGCAACUUUUUCGCGGUug ACCGCGAAAAAGUUGCGCG -2.2 -2.4 -3.9 -1 -2 5 -38.6 47.9 -3 -1 III 57.9 34.3 29.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2600 M15077 Reynolds Firefly luciferase 116160065 ACACAACUCCUCCGCGCAAcu UUGCGCGGAGGAGUUGUGU -0.9 -2.2 -2.7 2 0 6 -41.9 32 -1 2 II 57.9 31.8 24.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2601 M15077 Reynolds Firefly luciferase 116160065 UCAUCGUCUUUCCGUGCUCca GAGCACGGAAAGACGAUGA -2.4 -2.4 -1 0 3 3 -39.2 61.5 7.5 5 Ib 52.6 61.7 20.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2602 M15077 Reynolds Firefly luciferase 116160065 ACAACGGCGGCGGGAAGUUca AACUUCCCGCCGCCGUUGU -0.9 -2.2 1.6 1 1 10 -43.1 27.6 -6.3 4 II 63.2 39 18.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2603 M15077 Reynolds Firefly luciferase 116160065 CCAAAACAACAACGGCGGCgg GCCGCCGUUGUUGUUUUGG -3.4 -3.3 0.4 -2 1 7 -38.9 35.9 12.8 2 II 57.9 37.5 13.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2604 M15077 Reynolds Firefly luciferase 116160065 CGCAACUUUUUCGCGGUUGuu CAACCGCGAAAAAGUUGCG -2.1 -2.4 -3.5 0 -2 5 -35.8 56.9 -1.7 3 II 52.6 44 -1.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2605 M15077 Reynolds Firefly luciferase 116160065 CAACUUUUUCGCGGUUGUUac AACAACCGCGAAAAAGUUG -0.9 -2.1 -0.3 0 -1 5 -33.1 62.8 -8.3 4 II 42.1 43.3 -5.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2606 M15077 Reynolds Firefly luciferase 116160065 CGUCUUUCCGUGCUCCAAAac UUUGGAGCACGGAAAGACG -0.9 -2.4 -0.3 2 -3 3 -38.4 57.9 -1 3 II 52.6 37.2 -10.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2607 M15077 Reynolds Firefly luciferase 116160065 UCUUGGCCUUUAUGAGGAUcu AUCCUCAUAAAGGCCAAGA -1.1 -2.4 -0.5 -1 1 4 -37.2 55.1 -4 5 II 42.1 42.9 -12.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2608 M15077 Reynolds Firefly luciferase 116160065 UCGGUACUUCGUCCACAAAca UUUGUGGACGAAGUACCGA -0.9 -2.4 -0.7 0 -2 3 -37.7 57.4 1.7 4 II 47.4 40.6 -18 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2609 M15077 Reynolds Firefly luciferase 116160065 UCUUUCCGUGCUCCAAAACaa GUUUUGGAGCACGGAAAGA -2.2 -2.4 -1.4 0 2 3 -36.9 72.4 10.5 5 Ib 47.4 57 -27.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2610 M60857 Reynolds Cyclophilin B 829639 CUCUCCUGUAGCUAAGGCCac GGCCUUAGCUACAGGAGAG -3.3 -2.1 -1.1 0 1 4 -41.9 66 3.1 2 II 57.9 56.4 94.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2611 M60857 Reynolds Cyclophilin B 829639 UUUGUAGCCAAAUCCUUUCuc GAAAGGAUUUGGCUACAAA -2.4 -0.9 -0.5 1 3 3 -33.2 88.5 9.7 9 Ia 36.8 78.2 94.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2612 M60857 Reynolds Cyclophilin B 829639 AAUCCUUUCUCUCCUGUAGcu CUACAGGAGAGAAAGGAUU -2.1 -0.9 1.8 4 3 2 -36.1 86.2 3.1 6 Ia 42.1 59.6 93.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2613 M60857 Reynolds Cyclophilin B 829639 UAGCCAAAUCCUUUCUCUCcu GAGAGAAAGGAUUUGGCUA -2.4 -1.3 1.5 1 4 3 -36.1 80.1 10.4 5 Ib 42.1 70.6 93.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2614 M60857 Reynolds Cyclophilin B 829639 CACCGUAGAUGCUCUUUCCuc GGAAAGAGCAUCUACGGUG -3.3 -2.1 0.2 0 0 3 -38.7 64.9 3.1 3 II 52.6 52.1 93.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2615 M60857 Reynolds Cyclophilin B 829639 UCUCCGCCCUGGAUCAUGAag UCAUGAUCCAGGGCGGAGA -2.4 -2.4 -2.2 2 1 6 -43.7 55.2 -4 3 II 57.9 48 92.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2616 M60857 Reynolds Cyclophilin B 829639 GAAGUCUCCGCCCUGGAUCau GAUCCAGGGCGGAGACUUC -2.4 -2.4 -2.2 2 2 6 -43.6 56.3 7.4 2 II 63.2 52.2 92.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2617 M60857 Reynolds Cyclophilin B 829639 GUUCUCAUCGGGGAAGCGCuc GCGCUUCCCCGAUGAGAAC -3.4 -2.2 1 2 3 5 -42.5 48.1 7.4 3 II 63.2 50.5 92.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2618 M60857 Reynolds Cyclophilin B 829639 UGUAGCCAAAUCCUUUCUCuc GAGAAAGGAUUUGGCUACA -2.4 -2.1 1.4 0 4 3 -35.9 77.6 9.8 6 II 42.1 65.4 92.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2619 M60857 Reynolds Cyclophilin B 829639 GAUUACACGAUGGAAUUUGcu CAAAUUCCAUCGUGUAAUC -2.1 -2.4 2.9 1 1 2 -31.8 69 2.7 7 II 36.8 53.3 92.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2620 M60857 Reynolds Cyclophilin B 829639 ACACGAUGGAAUUUGCUGUuu ACAGCAAAUUCCAUCGUGU -2.2 -2.2 1.8 4 2 2 -35.9 70.4 3.7 6 II 42.1 54.4 91.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2621 M60857 Reynolds Cyclophilin B 829639 AUGCUCUUUCCUCCUGUGCca GCACAGGAGGAAAGAGCAU -3.4 -1.1 0.2 3 3 2 -40.4 75.1 10.5 6 Ib 52.6 64.3 90.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2622 M60857 Reynolds Cyclophilin B 829639 AAAUUAUCCACUGUUUUUGga CAAAAACAGUGGAUAAUUU -2.1 -0.9 2.2 3 4 2 -28.3 98.5 3 9 Ia 26.3 71.1 90.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2623 M60857 Reynolds Cyclophilin B 829639 UCAGUUUGAAGUUCUCAUCgg GAUGAGAACUUCAAACUGA -2.4 -2.4 0.4 1 2 1 -33.7 89.4 10.4 7 Ia 36.8 73.5 89.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2624 M60857 Reynolds Cyclophilin B 829639 CCUGGUGAAGUCUCCGCCCug GGGCGGAGACUUCACCAGG -3.3 -3.3 -0.8 -1 1 6 -45.3 39.9 3.1 1 II 68.4 50.5 89 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2625 M60857 Reynolds Cyclophilin B 829639 GAAGCGCUCACCGUAGAUGcu CAUCUACGGUGAGCGCUUC -2.1 -2.4 -0.7 1 2 4 -40.3 48.6 -2.4 2 II 57.9 46.2 89 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2626 M60857 Reynolds Cyclophilin B 829639 UGAAGUCCUUGAUUACACGau CGUGUAAUCAAGGACUUCA -2.4 -2.1 1.5 0 4 2 -35.1 74.4 2.3 5 Ib 42.1 67.8 88.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2627 M60857 Reynolds Cyclophilin B 829639 UCCGCCCUGGAUCAUGAAGuc CUUCAUGAUCCAGGGCGGA -2.1 -2.4 -1.4 1 1 6 -42.2 58.8 7.7 1 II 57.9 49.3 88.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2628 M60857 Reynolds Cyclophilin B 829639 GCCAAAUCCUUUCUCUCCUgu AGGAGAGAAAGGAUUUGGC -2.1 -3.4 2.3 2 0 3 -38.1 62.7 6.5 3 II 47.4 40.6 88.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2629 M60857 Reynolds Cyclophilin B 829639 UAUCCACUGUUUUUGGAACag GUUCCAAAAACAGUGGAUA -2.2 -1.3 -2.5 2 4 2 -33.3 85.9 12.8 4 Ib 36.8 62.7 88.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2630 M60857 Reynolds Cyclophilin B 829639 AUCAUGAAGUCCUUGAUUAca UAAUCAAGGACUUCAUGAU -1.3 -1.1 0.7 2 0 2 -32.9 79.7 -6.1 7 II 31.6 55.5 87.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2631 M60857 Reynolds Cyclophilin B 829639 AUCUCCCCUGGUGAAGUCUcc AGACUUCACCAGGGGAGAU -2.1 -1.1 -2.5 1 1 4 -41.8 63 -1 4 II 52.6 50.3 87.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2632 M60857 Reynolds Cyclophilin B 829639 UUGAUUACACGAUGGAAUUug AAUUCCAUCGUGUAAUCAA -0.9 -0.9 1.5 -1 0 2 -31.8 83 -4 7 II 31.6 65.9 87.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2633 M60857 Reynolds Cyclophilin B 829639 GUCCUUGAUUACACGAUGGaa CCAUCGUGUAAUCAAGGAC -3.3 -2.2 0.9 1 1 2 -36.5 63.6 -2.6 4 II 47.4 51.6 87.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2634 M60857 Reynolds Cyclophilin B 829639 AAGUCCUUGAUUACACGAUgg AUCGUGUAAUCAAGGACUU -1.1 -0.9 1.5 3 1 2 -34.1 78.1 -3.5 6 II 36.8 55.8 86.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2635 M60857 Reynolds Cyclophilin B 829639 UCUCAUCGGGGAAGCGCUCac GAGCGCUUCCCCGAUGAGA -2.4 -2.4 1 1 3 5 -43.9 39.5 7.5 4 Ib 63.2 54.7 86.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2636 M60857 Reynolds Cyclophilin B 829639 UUACACGAUGGAAUUUGCUgu AGCAAAUUCCAUCGUGUAA -2.1 -0.9 1.1 1 4 2 -33.8 71.2 -1.5 7 II 36.8 68.7 86.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2637 M60857 Reynolds Cyclophilin B 829639 AGUUUGAAGUUCUCAUCGGgg CCGAUGAGAACUUCAAACU -3.3 -2.1 0.1 2 4 3 -34.9 69.4 -2.4 6 Ia 42.1 59.5 85.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2638 M60857 Reynolds Cyclophilin B 829639 CAAAUCCUUUCUCUCCUGUag ACAGGAGAGAAAGGAUUUG -2.2 -2.1 2.3 -1 0 2 -35.7 75.9 -0.6 5 II 42.1 47.9 84.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2639 M60857 Reynolds Cyclophilin B 829639 UCUUUCCUCCUGUGCCAUCuc GAUGGCACAGGAGGAAAGA -2.4 -2.4 3 0 2 3 -40.6 67.9 7.4 6 Ib 52.6 59.1 84.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2640 M60857 Reynolds Cyclophilin B 829639 UUUGAAGUUCUCAUCGGGGaa CCCCGAUGAGAACUUCAAA -3.3 -0.9 0.1 0 6 5 -37.2 65.1 0.1 7 Ia 47.4 72.9 84.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2641 M60857 Reynolds Cyclophilin B 829639 UAAGGCCACAAAAUUAUCCac GGAUAAUUUUGUGGCCUUA -3.3 -1.3 0.9 1 5 4 -33.5 81.8 9.4 7 II 36.8 80.6 83.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2642 M60857 Reynolds Cyclophilin B 829639 UCAUCGGGGAAGCGCUCACcg GUGAGCGCUUCCCCGAUGA -2.2 -2.4 0.7 0 3 5 -43.7 49.5 12.1 6 II 63.2 55.7 83.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2643 M60857 Reynolds Cyclophilin B 829639 UGAAGUUCUCAUCGGGGAAgc UUCCCCGAUGAGAACUUCA -0.9 -2.1 0.1 0 0 5 -38.7 63.9 4 6 II 47.4 48.4 83.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2644 M60857 Reynolds Cyclophilin B 829639 UGUUUUUGUAGCCAAAUCCuu GGAUUUGGCUACAAAAACA -3.3 -2.1 -1.3 1 3 3 -33 93.5 7.5 8 Ia 36.8 79.5 83.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2645 M60857 Reynolds Cyclophilin B 829639 CCCUGGAUCAUGAAGUCCUug AGGACUUCAUGAUCCAGGG -2.1 -3.3 -2.1 0 -2 3 -40.7 49.8 -8.6 2 III 52.6 46 82.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2646 M60857 Reynolds Cyclophilin B 829639 UUUUUGUAGCCAAAUCCUUuc AAGGAUUUGGCUACAAAAA -0.9 -0.9 -1.3 2 2 3 -31.7 78.3 -8.9 7 II 31.6 69.2 81.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2647 M60857 Reynolds Cyclophilin B 829639 UAGCUAAGGCCACAAAAUUau AAUUUUGUGGCCUUAGCUA -0.9 -1.3 -1.6 2 0 4 -34.3 61.5 -3.9 5 II 36.8 60.3 81.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2648 M60857 Reynolds Cyclophilin B 829639 CUCCCCUGGUGAAGUCUCCgc GGAGACUUCACCAGGGGAG -3.3 -2.1 -1.6 1 0 4 -44 46.8 2.8 1 II 63.2 46.7 80.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2649 M60857 Reynolds Cyclophilin B 829639 UCCUCCUGUGCCAUCUCCCcu GGGAGAUGGCACAGGAGGA -3.3 -2.4 3 1 4 3 -45.4 64.1 2.4 4 II 63.2 66.8 80.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2650 M60857 Reynolds Cyclophilin B 829639 AUCGGGGAAGCGCUCACCGua CGGUGAGCGCUUCCCCGAU -2.4 -1.1 -1.2 1 5 5 -44.9 41.1 2.4 2 II 68.4 60.6 80.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2651 M60857 Reynolds Cyclophilin B 829639 UGGAAUUUGCUGUUUUUGUag ACAAAAACAGCAAAUUCCA -2.2 -2.1 4.5 2 1 2 -31.4 91.1 1.1 7 II 31.6 65.2 78.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2652 M60857 Reynolds Cyclophilin B 829639 AUUUGCUGUUUUUGUAGCCaa GGCUACAAAAACAGCAAAU -3.3 -1.1 -1.9 1 5 3 -32.8 83.4 10.4 5 Ia 36.8 67.3 77.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2653 M60857 Reynolds Cyclophilin B 829639 UUCUCUCCUGUAGCUAAGGcc CCUUAGCUACAGGAGAGAA -3.3 -0.9 -0.7 0 3 2 -38.5 70.7 0 5 Ib 47.4 67.9 77.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2654 M60857 Reynolds Cyclophilin B 829639 CCCCUGGUGAAGUCUCCGCcc GCGGAGACUUCACCAGGGG -3.4 -3.3 -0.8 1 0 4 -45.3 44.8 7.7 2 II 68.4 44.7 76.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2655 M60857 Reynolds Cyclophilin B 829639 CUCCUGUGCCAUCUCCCCUgg AGGGGAGAUGGCACAGGAG -2.1 -2.1 3 2 0 4 -45.1 56.2 4.1 2 III 63.2 48.7 76.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2656 M60857 Reynolds Cyclophilin B 829639 UCCUUUCUCUCCUGUAGCUaa AGCUACAGGAGAGAAAGGA -2.1 -2.4 1.6 0 1 2 -39.6 70.6 -8.7 5 II 47.4 52.1 75.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2657 M60857 Reynolds Cyclophilin B 829639 AUUAUCCACUGUUUUUGGAac UCCAAAAACAGUGGAUAAU -2.4 -1.1 -2.3 2 3 2 -32.2 90.5 1.6 5 II 31.6 51.9 75.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2658 M60857 Reynolds Cyclophilin B 829639 AGAUGCUCUUUCCUCCUGUgc ACAGGAGGAAAGAGCAUCU -2.2 -2.1 1.1 2 2 2 -39.4 67.5 -1.6 6 II 47.4 54.4 74.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2659 M60857 Reynolds Cyclophilin B 829639 CUGGAUCAUGAAGUCCUUGau CAAGGACUUCAUGAUCCAG -2.1 -2.1 -2.1 -1 0 2 -37.1 56.1 5.3 2 II 47.4 52 74.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2660 M60857 Reynolds Cyclophilin B 829639 UGUGCCAUCUCCCCUGGUGaa CACCAGGGGAGAUGGCACA -2.1 -2.1 -1.5 1 3 4 -44.9 58.8 -2.3 3 II 63.2 57.3 73.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2661 M60857 Reynolds Cyclophilin B 829639 GUAGUGCUUCAGUUUGAAGuu CUUCAAACUGAAGCACUAC -2.1 -2.2 -2 0 2 2 -34.4 70.1 4.6 2 II 42.1 46.7 73.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2662 M60857 Reynolds Cyclophilin B 829639 CGCUCACCGUAGAUGCUCUuu AGAGCAUCUACGGUGAGCG -2.1 -2.4 -0.9 0 -2 3 -41.5 51.7 -3.9 1 III 57.9 32.3 71.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2663 M60857 Reynolds Cyclophilin B 829639 GAAUUUGCUGUUUUUGUAGcc CUACAAAAACAGCAAAUUC -2.1 -2.4 2.8 0 2 2 -29.4 90.1 5.4 6 II 31.6 55.7 71.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2664 M60857 Reynolds Cyclophilin B 829639 UUUCCUCCUGUGCCAUCUCcc GAGAUGGCACAGGAGGAAA -2.4 -0.9 3 1 4 3 -40.6 67.4 9.8 5 Ib 52.6 67.3 70.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2665 M60857 Reynolds Cyclophilin B 829639 AGUGCUUCAGUUUGAAGUUcu AACUUCAAACUGAAGCACU -0.9 -2.1 -2.5 1 1 2 -34 72 -1 3 II 36.8 50.5 69.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2666 M60857 Reynolds Cyclophilin B 829639 UUGCUGUUUUUGUAGCCAAau UUGGCUACAAAAACAGCAA -0.9 -0.9 -1.9 2 0 3 -33.8 73.1 -3.8 5 II 36.8 60.1 68 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2667 M60857 Reynolds Cyclophilin B 829639 AAGUUCUCAUCGGGGAAGCgc GCUUCCCCGAUGAGAACUU -3.4 -0.9 1.2 1 3 5 -39.7 61.7 5.1 6 Ia 52.6 57.5 67.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2668 M60857 Reynolds Cyclophilin B 829639 GGAUCAUGAAGUCCUUGAUua AUCAAGGACUUCAUGAUCC -1.1 -3.3 -0.4 1 -1 2 -36.4 69.8 1.5 4 II 42.1 32.5 66.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2669 M60857 Reynolds Cyclophilin B 829639 AGCGCUCACCGUAGAUGCUcu AGCAUCUACGGUGAGCGCU -2.1 -2.1 -0.9 1 1 4 -42.5 46.7 -3.5 1 II 57.9 39.4 64.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2670 M60857 Reynolds Cyclophilin B 829639 CAUGAAGUCCUUGAUUACAcg UGUAAUCAAGGACUUCAUG -2.1 -2.1 1.6 0 -2 2 -33.7 61 0 4 II 36.8 45.2 63.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2671 M60857 Reynolds Cyclophilin B 829639 CUCCUGUAGCUAAGGCCACaa GUGGCCUUAGCUACAGGAG -2.2 -2.1 -5.8 1 0 4 -41.7 39.8 2.8 1 II 57.9 45.8 60.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2672 M60857 Reynolds Cyclophilin B 829639 GUAGAUGCUCUUUCCUCCUgu AGGAGGAAAGAGCAUCUAC -2.1 -2.2 0.4 0 1 2 -38.6 62.1 1.8 4 II 47.4 52.5 58.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2673 M60857 Reynolds Cyclophilin B 829639 CCGUAGAUGCUCUUUCCUCcu GAGGAAAGAGCAUCUACGG -2.4 -3.3 0.6 0 0 3 -38.9 57 8.1 3 II 52.6 48.8 58.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2674 M60857 Reynolds Cyclophilin B 829639 GCUCUUUCCUCCUGUGCCAuc UGGCACAGGAGGAAAGAGC -2.1 -3.4 1.9 2 -1 3 -42.6 50.4 -8.5 2 II 57.9 32.9 55.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2675 M60857 Reynolds Cyclophilin B 829639 AGGCCACAAAAUUAUCCACug GUGGAUAAUUUUGUGGCCU -2.2 -2.1 0.9 2 2 4 -35.6 68.3 12.7 3 II 42.1 50.6 55 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2676 M60857 Reynolds Cyclophilin B 829639 UGUAGCUAAGGCCACAAAAuu UUUUGUGGCCUUAGCUACA -0.9 -2.1 -5.9 1 -1 4 -36.6 68 -3.7 5 II 42.1 52.5 52 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2677 M60857 Reynolds Cyclophilin B 829639 CGCCCUGGAUCAUGAAGUCcu GACUUCAUGAUCCAGGGCG -2.4 -2.4 1 -1 -1 5 -41.1 40.7 3.1 0 II 57.9 34.6 51.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2678 M60857 Reynolds Cyclophilin B 829639 CUCACCGUAGAUGCUCUUUcc AAAGAGCAUCUACGGUGAG -0.9 -2.1 -0.9 -1 -3 3 -37.5 67.2 -0.7 4 III 47.4 42 50.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2679 M60857 Reynolds Cyclophilin B 829639 CAAAAUUAUCCACUGUUUUug AAAACAGUGGAUAAUUUUG -0.9 -2.1 2.1 0 -1 2 -28.3 83.2 -0.9 6 II 26.3 54.4 49.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2680 M60857 Reynolds Cyclophilin B 829639 AGUCUCCGCCCUGGAUCAUga AUGAUCCAGGGCGGAGACU -1.1 -2.1 -2.2 2 1 6 -43.5 42.2 -3.3 2 II 57.9 31.5 48.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2681 M60857 Reynolds Cyclophilin B 829639 UGGUGAAGUCUCCGCCCUGga CAGGGCGGAGACUUCACCA -2.1 -2.1 -0.9 -1 2 6 -44.1 41.2 0.1 4 Ib 63.2 55.7 46.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2682 M60857 Reynolds Cyclophilin B 829639 CCUUGAUUACACGAUGGAAuu UUCCAUCGUGUAAUCAAGG -0.9 -3.3 1.5 0 -3 2 -35.2 55.3 -5.8 3 II 42.1 28.4 45.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2683 M60857 Reynolds Cyclophilin B 829639 UGCUUCAGUUUGAAGUUCUca AGAACUUCAAACUGAAGCA -2.1 -2.1 -2.5 0 0 2 -34.2 76.1 -6.6 6 II 36.8 61.7 45.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2684 M60857 Reynolds Cyclophilin B 829639 CCAUCUCCCCUGGUGAAGUcu ACUUCACCAGGGGAGAUGG -2.2 -3.3 -2.5 0 -1 4 -42.7 50 -3.6 0 III 57.9 37.7 41.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2685 M60857 Reynolds Cyclophilin B 829639 GUGAAGUCUCCGCCCUGGAuc UCCAGGGCGGAGACUUCAC -2.4 -2.2 -1.9 1 -1 6 -44.4 42.5 -1 2 II 63.2 37.1 41.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2686 M60857 Reynolds Cyclophilin B 829639 CUUCAGUUUGAAGUUCUCAuc UGAGAACUUCAAACUGAAG -2.1 -2.1 -2.1 1 -1 1 -33.2 69.5 1.6 4 II 36.8 51.1 41.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2687 M60857 Reynolds Cyclophilin B 829639 GCCACAAAAUUAUCCACUGuu CAGUGGAUAAUUUUGUGGC -2.1 -3.4 2 0 0 3 -34.4 58.6 0 2 II 42.1 42.8 39.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2688 M60857 Reynolds Cyclophilin B 829639 GCUAAGGCCACAAAAUUAUcc AUAAUUUUGUGGCCUUAGC -1.1 -3.4 1.2 1 -2 4 -33.3 56.5 -6.2 6 III 36.8 38.6 32.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2689 M60857 Reynolds Cyclophilin B 829639 CUUUCUCUCCUGUAGCUAAgg UUAGCUACAGGAGAGAAAG -0.9 -2.1 1.6 0 -3 2 -36.1 72.7 -5.8 4 II 42.1 39.5 30.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2690 M60857 Reynolds Cyclophilin B 829639 CCUGUGCCAUCUCCCCUGGug CCAGGGGAGAUGGCACAGG -3.3 -3.3 -1 -1 0 4 -46 43.3 1.1 1 II 68.4 39 21.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2691 M60857 Reynolds Cyclophilin B 829639 CCGUAGUGCUUCAGUUUGAag UCAAACUGAAGCACUACGG -2.4 -3.3 0.5 0 -4 3 -37.1 47.5 -8 4 III 47.4 32.9 18.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2692 M60857 Reynolds Cyclophilin B 829639 UGCCAUCUCCCCUGGUGAAgu UUCACCAGGGGAGAUGGCA -0.9 -2.1 -1.5 1 -1 4 -43.9 48.8 -5.8 2 II 57.9 35.9 17.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2693 M60857 Reynolds Cyclophilin B 829639 CACAAAAUUAUCCACUGUUuu AACAGUGGAUAAUUUUGUG -0.9 -2.1 -0.1 -1 -2 2 -30.8 70.1 -3.2 5 II 31.6 50.7 16.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2694 M60857 Reynolds Cyclophilin B 829639 CCUGUAGCUAAGGCCACAAaa UUGUGGCCUUAGCUACAGG -0.9 -3.3 -7.1 -1 -3 4 -40.2 44 -3.5 3 III 52.6 32.5 16 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2695 M60857 Reynolds Cyclophilin B 829639 GCUGUUUUUGUAGCCAAAUcc AUUUGGCUACAAAAACAGC -1.1 -3.4 -1.3 1 -2 3 -32.8 63.4 -4 2 II 36.8 41.5 13.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2696 M60857 Reynolds Cyclophilin B 829639 GAUGGAAUUUGCUGUUUUUgu AAAAACAGCAAAUUCCAUC -0.9 -2.4 4.5 -1 -1 2 -30.6 70.2 -6.3 4 II 31.6 38.5 7.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2697 M60857 Reynolds Cyclophilin B 829639 ACGAUGGAAUUUGCUGUUUuu AAACAGCAAAUUCCAUCGU -0.9 -2.2 2.7 1 -1 2 -33.4 63.7 -1 6 II 36.8 47.3 7.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2698 M60857 Reynolds Cyclophilin B 829639 GGGAAGCGCUCACCGUAGAug UCUACGGUGAGCGCUUCCC -2.4 -3.3 -0.1 1 -3 4 -43.7 31.4 -1 1 III 63.2 23.1 2.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2699 M60857 Reynolds Cyclophilin B 829639 CGGGGAAGCGCUCACCGUAga UACGGUGAGCGCUUCCCCG -1.3 -2.4 -0.6 0 -4 5 -44.9 24.4 -2.7 0 III 68.4 28.7 -9.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2700 - Reynolds RenillaLuc / CACAACAUGUCGCCAUAAAua UUUAUGGCGACAUGUUGUG -0.9 -2.1 -2.8 0 -4 4 -34.8 58.4 -3 3 II 42.1 32.3 29.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2701 - Reynolds RenillaLuc / UUCAAACCAUGCAGUAAGAua UCUUACUGCAUGGUUUGAA -2.4 -0.9 0.8 -1 0 2 -34.5 64 -6 6 II 36.8 50.5 52.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2702 - Reynolds RenillaLuc / AAUCACAUCUACUACACUUuc AAGUGUAGUAGAUGUGAUU -0.9 -0.9 3.3 3 2 1 -32.8 80.1 -1.3 6 II 31.6 61.2 87.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2703 - Reynolds RenillaLuc / GUUCUAACUUUCUCAUGAUuu AUCAUGAGAAAGUUAGAAC -1.1 -2.2 1.1 1 0 1 -31.6 70 -6.3 4 II 31.6 40.4 47.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2704 - Reynolds RenillaLuc / CAAGAUAUGCUGCAAAUUCuu GAAUUUGCAGCAUAUCUUG -2.4 -2.1 2.2 0 0 2 -32.4 66.3 10.5 5 II 36.8 60.8 84.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2705 - Reynolds RenillaLuc / UAAUGUUGGACGACGAACUuc AGUUCGUCGUCCAACAUUA -2.1 -1.3 0.5 2 2 2 -35.5 75.5 -8.9 8 II 42.1 74 66.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2706 - Reynolds RenillaLuc / AUCAUCACUUGCACGUAGAua UCUACGUGCAAGUGAUGAU -2.4 -1.1 -0.4 1 0 2 -36.6 70.2 -8.7 6 II 42.1 52.7 89.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2707 - Reynolds RenillaLuc / CAUUUCAUCAGGUGCAUCUuc AGAUGCACCUGAUGAAAUG -2.1 -2.1 1.6 -1 -1 2 -35.9 81 -6 7 II 42.1 54.3 63.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2708 - Reynolds RenillaLuc / UCAUCCGUUUCCUUUGUUCug GAACAAAGGAAACGGAUGA -2.4 -2.4 2.6 0 3 3 -34.9 84.9 5 7 II 42.1 65.2 84.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2709 - Reynolds RenillaLuc / UCCUUCUUCAGAUUUGAUCaa GAUCAAAUCUGAAGAAGGA -2.4 -2.4 0 2 2 2 -34 96.7 9.7 7 Ib 36.8 70.1 90.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2710 - Reynolds RenillaLuc / UAUUAGGAAACUUCUUGGCac GCCAAGAAGUUUCCUAAUA -3.4 -1.3 1.8 0 5 3 -33.6 88.5 10.8 9 Ia 36.8 74.5 72.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2711 - Reynolds RenillaLuc / AAUGGUUCAAGAUAUGCUGca CAGCAUAUCUUGAACCAUU -2.1 -0.9 1.1 2 4 2 -33.6 79.8 0 6 Ia 36.8 69 83.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2712 NM_031313 Reynolds SEAP 7124 AGAUGAUGAGGUUCUUGGCgg GCCAAGAACCUCAUCAUCU -3.4 -2.1 0.8 2 4 3 -38.4 70.8 10.4 5 Ia 47.4 56.9 90.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2713 NM_031313 Reynolds SEAP 7124 CUGUAGUCAUCUGGGUACUca AGUACCCAGAUGACUACAG -2.1 -2.1 0.9 -1 -2 3 -38.6 57 -2.6 4 II 47.4 42.7 1.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2714 NM_031313 Reynolds SEAP 7124 GUAUAGGAGGACCGUGUAGgc CUACACGGUCCUCCUAUAC -2.1 -2.2 -0.7 0 1 3 -39.3 48.9 5.1 6 II 52.6 41.8 21.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2715 NM_031313 Reynolds SEAP 7124 AUAGCCUGGACCGUUUCCGua CGGAAACGGUCCAGGCUAU -2.4 -1.1 -3.5 3 6 3 -41.1 61.7 -2.4 4 Ib 57.9 67.7 80.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2716 NM_031313 Reynolds SEAP 7124 ACAUAGCCUGGACCGUUUCcg GAAACGGUCCAGGCUAUGU -2.4 -2.2 -1.2 1 2 3 -39.7 56.7 12.5 5 Ib 52.6 52.9 6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2717 NM_031313 Reynolds SEAP 7124 CAUGACGUGCGCUAUGAAGgu CUUCAUAGCGCACGUCAUG -2.1 -2.1 1.2 0 0 4 -37.8 56.9 -1.7 4 II 52.6 45.1 16.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2718 NM_031313 Reynolds SEAP 7124 UAUAGGAGGACCGUGUAGGcc CCUACACGGUCCUCCUAUA -3.3 -1.3 -0.7 1 5 3 -40.4 64.7 -2.4 8 Ia 52.6 72 62.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2719 U47296 Reynolds FireflyLuc 116160065 UAUCAUGUCUGCUCGAAGCgg GCUUCGAGCAGACAUGAUA -3.4 -1.3 -1.2 2 4 2 -38 79.1 7.8 6 Ia 47.4 73.2 97.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2720 U47296 Reynolds FireflyLuc 116160065 UUUUAGAAUCCAUGAUAAUaa AUUAUCAUGGAUUCUAAAA -1.1 -0.9 2 -1 1 2 -28.3 81.8 -3.6 8 II 21.1 60.4 55.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2721 U47296 Reynolds FireflyLuc 116160065 CAAAUAUCCGAGUGUAGUAaa UACUACACUCGGAUAUUUG -1.3 -2.1 1.4 0 -2 3 -33.4 68.6 -3.5 5 II 36.8 43.9 38.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2722 U47296 Reynolds FireflyLuc 116160065 GGAUUGUUUACAUAACCGGac CCGGUUAUGUAAACAAUCC -3.3 -3.3 0.3 1 2 4 -33.9 67.5 -2.4 5 II 42.1 55.1 41.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2723 U47296 Reynolds FireflyLuc 116160065 CGCUUCCGGAUUGUUUACAua UGUAAACAAUCCGGAAGCG -2.1 -2.4 0 0 -3 4 -36.3 61.8 -0.4 3 III 47.4 34.4 9.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2724 U47296 Reynolds FireflyLuc 116160065 GGCGUUGGUCGCUUCCGGAuu UCCGGAAGCGACCAACGCC -2.4 -3.3 -2.3 0 -1 4 -44.8 39.5 -3.8 0 III 68.4 28.8 89.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2725 U47296 Reynolds FireflyLuc 116160065 GUACUUAAUCAGAGACUUCag GAAGUCUCUGAUUAAGUAC -2.4 -2.2 0.8 0 1 1 -33.1 64.9 7.1 5 II 36.8 54.6 34.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2726 U47296 Reynolds FireflyLuc 116160065 UUUGUAUUCAGCCCAUAUCgu GAUAUGGGCUGAAUACAAA -2.4 -0.9 1.3 2 3 4 -34 89.8 7.5 8 Ia 36.8 76.9 91.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2727 U47296 Reynolds FireflyLuc 116160065 UACUUAAUCAGAGACUUCAgg UGAAGUCUCUGAUUAAGUA -2.1 -1.3 0.8 1 0 1 -33 84.3 -3.8 9 II 31.6 67.5 91.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2728 NM_020548 Reynolds DBI 1622 GCUCAUUCCAGGCAUCCCAcu UGGGAUGCCUGGAAUGAGC -2.1 -3.4 -0.3 3 -1 3 -42.9 50.6 1.4 3 II 57.9 39.4 4.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2729 NM_020548 Reynolds DBI 1622 GUAAGCUUUCAUGGCAUCUuc AGAUGCCAUGAAAGCUUAC -2.1 -2.2 0.3 0 0 3 -35.9 67.9 1.4 5 II 42.1 49.9 -9.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2730 NM_020548 Reynolds DBI 1622 AACAAGGCAUUGUCUCAGUuu ACUGAGACAAUGCCUUGUU -2.2 -0.9 -1 1 1 3 -36.6 64 -1.3 5 II 42.1 53.3 6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2731 NM_020548 Reynolds DBI 1622 GGAAAGUCAGUAAUCGUUUua AAACGAUUACUGACUUUCC -0.9 -3.3 1.9 1 -1 2 -32.7 61.9 -1.5 5 II 36.8 46.5 -18.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2732 NM_020548 Reynolds DBI 1622 ACUCAAGGAAAGUCAGUAAuc UUACUGACUUUCCUUGAGU -0.9 -2.2 -0.7 2 -1 2 -34.6 61.7 1.3 7 II 36.8 39.7 -8.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2733 NM_020548 Reynolds DBI 1622 UAAGCUUUCAUGGCAUCUUcc AAGAUGCCAUGAAAGCUUA -0.9 -1.3 0.3 2 2 3 -34.6 78.8 -4 7 II 36.8 70.8 50.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2734 NM_020548 Reynolds DBI 1622 UUGUUGAUGUAAGCUUUCAug UGAAAGCUUACAUCAACAA -2.1 -0.9 1.3 1 0 2 -32.1 82.1 -1.5 8 II 31.6 64.7 33.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2735 NM_020548 Reynolds DBI 1622 UCUUUAGCUCUUCUACUUUgu AAAGUAGAAGAGCUAAAGA -0.9 -2.4 -0.2 0 1 2 -32.5 83.9 3.8 8 II 31.6 58.9 71.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2736 NM_020548 Reynolds DBI 1622 UAUUUUUUCUUUAGCUCUUcu AAGAGCUAAAGAAAAAAUA -0.9 -1.3 5.2 1 2 2 -27.5 100.6 -3.5 8 II 21.1 70.9 68 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2737 X75932 Reynolds PLK 5347 GCACUUGGCAAAGCCGCCCuu GGGCGGCUUUGCCAAGUGC -3.3 -3.4 -4.2 2 2 7 -44.6 38.9 9.7 2 II 68.4 50.3 30.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2738 X75932 Reynolds PLK 5347 GGAUAUUUCCAUGGACAUCuu GAUGUCCAUGGAAAUAUCC -2.4 -3.3 -1.3 1 0 2 -35.5 65.8 15.4 3 II 42.1 46.1 43.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2739 X75932 Reynolds PLK 5347 CACAUCCACCUCGAAACUGug CAGUUUCGAGGUGGAUGUG -2.1 -2.1 1.1 0 0 2 -38.3 50 -4.4 3 II 52.6 47.6 52.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2740 X75932 Reynolds PLK 5347 GGAAUACUGUAUUCAUUCUuc AGAAUGAAUACAGUAUUCC -2.1 -3.3 -0.8 1 -1 2 -31.9 77.9 1.4 4 II 31.6 40 58 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2741 X75932 Reynolds PLK 5347 AUGAGGCGUGUUGAGUCAUug AUGACUCAACACGCCUCAU -1.1 -1.1 1.3 1 1 4 -38.6 50.4 -1 4 II 47.4 48 58.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2742 X75932 Reynolds PLK 5347 UCAUGUAAUUGCGGAAAUAuu UAUUUCCGCAAUUACAUGA -1.3 -2.4 1.7 -1 -1 4 -31.9 63 -6.1 6 II 31.6 51.2 57.1 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2743 X75932 Reynolds PLK 5347 AGAGACUUAGGCACAAUCUug AGAUUGUGCCUAAGUCUCU -2.1 -2.1 -1.6 2 1 3 -37.2 65.5 -6.2 5 II 42.1 58.2 68.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2744 X75932 Reynolds PLK 5347 UUCACCUCCAGAUCUUCAUuc AUGAAGAUCUGGAGGUGAA -1.1 -0.9 0.4 2 1 2 -37.4 86.7 -4 7 II 42.1 62.8 55 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2745 X75932 Reynolds PLK 5347 UUAGGCAAGAAGUCUCAAAag UUUGAGACUUCUUGCCUAA -0.9 -0.9 -0.3 1 0 3 -34.5 72.4 -1.5 7 II 36.8 60.5 82.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2746 X75932 Reynolds PLK 5347 UAUUUAAGGAGGGUGAUCUuc AGAUCACCCUCCUUAAAUA -2.1 -1.3 1.7 1 3 3 -35.2 85.2 -1.6 10 II 36.8 70.6 72.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2747 NM_002046 Reynolds GAPDH 2597 CCCUUUUGGCUCCCCCCUGca CAGGGGGGAGCCAAAAGGG -2.1 -3.3 -2.3 1 -1 6 -45.4 45.5 -2 1 II 68.4 43.8 -24.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2748 NM_002046 Reynolds GAPDH 2597 AGGGGGCAGAGAUGAUGACcc GUCAUCAUCUCUGCCCCCU -2.2 -2.1 2.7 1 2 6 -43.2 37.5 7.4 2 II 57.9 41.5 69.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2749 NM_002046 Reynolds GAPDH 2597 GAACAUGGGGGCAUCAGCAga UGCUGAUGCCCCCAUGUUC -2.1 -2.4 -0.6 2 1 6 -42.7 42.1 -3.7 3 II 57.9 43.2 12.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2750 NM_002046 Reynolds GAPDH 2597 UCAUGGUUCACACCCAUGAcg UCAUGGGUGUGAACCAUGA -2.4 -2.4 -7 2 0 3 -39.4 67 -3.7 7 II 47.4 61.6 60.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2751 NM_002046 Reynolds GAPDH 2597 UGAGGCUGUUGUCAUACUUcu AAGUAUGACAACAGCCUCA -0.9 -2.1 0.8 1 1 3 -37 67.8 1.5 5 II 42.1 57.6 94.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2752 NM_002046 Reynolds GAPDH 2597 GGAGGCAUUGCUGAUGAUCuu GAUCAUCAGCAAUGCCUCC -2.4 -3.3 0.4 0 0 3 -39.8 48.2 8.1 2 II 52.6 44.6 70.8 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2753 NM_002046 Reynolds GAPDH 2597 GCUAAGCAGUUGGUGGUGCag GCACCACCAACUGCUUAGC -3.4 -3.4 -1.3 1 2 2 -41.2 43.7 12.4 2 II 57.9 38.9 38.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2754 NM_002046 Reynolds GAPDH 2597 GGAUGACCUUGGCCAGGGGug CCCCUGGCCAAGGUCAUCC -3.3 -3.3 -3.6 0 2 4 -46 33.4 2.4 0 II 68.4 30.5 -2.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2755 NM_002046 Reynolds GAPDH 2597 CACGAUACCAAAGUUGUCAug UGACAACUUUGGUAUCGUG -2.1 -2.1 1.1 0 -2 2 -34.9 66.2 1.6 5 II 42.1 49.9 43 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2756 NM_002046 Reynolds GAPDH 2597 ACUGUGGUCAUGAGUCCUUcc AAGGACUCAUGACCACAGU -0.9 -2.2 -0.7 1 1 2 -39.3 51.3 -6.6 6 II 47.4 50.3 -17.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2757 NM_002046 Reynolds GAPDH 2597 UGAUGACCCUUUUGGCUCCcc GGAGCCAAAAGGGUCAUCA -3.3 -2.1 -1.5 0 3 3 -40.3 64.3 10.4 5 Ib 52.6 61.6 88.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2758 NM_002046 Reynolds GAPDH 2597 GAGAUGAUGACCCUUUUGGcu CCAAAAGGGUCAUCAUCUC -3.3 -2.4 -0.6 1 2 3 -37.1 72.4 0 6 II 47.4 55.9 93.9 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2759 NM_002046 Reynolds GAPDH 2597 UUCACACCCAUGACGAACAug UGUUCGUCAUGGGUGUGAA -2.1 -0.9 -1.5 1 0 3 -38.4 66.6 -6.3 5 II 47.4 62 80.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2760 NM_002046 Reynolds GAPDH 2597 UACUUCUCAUGGUUCACACcc GUGUGAACCAUGAGAAGUA -2.2 -1.3 0.9 1 4 2 -36.1 92 9.7 7 Ia 42.1 68.6 92.7 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2761 NM_002046 Reynolds GAPDH 2597 UUGUCAUACUUCUCAUGGUuc ACCAUGAGAAGUAUGACAA -2.2 -0.9 -0.3 2 2 2 -35 80.6 -6.3 6 II 36.8 63.6 92.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2762 NM_002046 Reynolds GAPDH 2597 UGUUGUCAUACUUCUCAUGgu CAUGAGAAGUAUGACAACA -2.1 -2.1 0 0 2 1 -33.8 86.5 0.7 6 Ib 36.8 65.5 92.4 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2763 NM_002046 Reynolds GAPDH 2597 CUUGAGGCUGUUGUCAUACuu GUAUGACAACAGCCUCAAG -2.2 -2.1 0.3 -1 1 3 -37 60.9 13.5 5 II 47.4 55.1 77.6 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2764 NM_002046 Reynolds GAPDH 2597 AUCUUGAGGCUGUUGUCAUac AUGACAACAGCCUCAAGAU -1.1 -1.1 0.3 2 2 3 -37 71.3 -1.6 6 II 42.1 52.3 58.3 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2765 NM_002046 Reynolds GAPDH 2597 UGAUCUUGAGGCUGUUGUCau GACAACAGCCUCAAGAUCA -2.4 -2.1 1.3 0 3 3 -38.3 76.1 5.1 6 Ia 47.4 62.6 94.2 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2766 NM_002046 Reynolds GAPDH 2597 UCAUGGAUGACCUUGGCCAgg UGGCCAAGGUCAUCCAUGA -2.1 -2.4 -3.5 1 2 4 -41.7 63 -6.1 6 II 52.6 61.3 91.5 branched DNA (bDNA) technology HEK293 100nM 24h Rational siRNA design for RNA interference. 14758366 2004 Short-interfering RNAs suppress gene expression through a highly regulated enzyme-mediated process called RNA interference (RNAi). RNAi involves multiple RNA-protein interactions characterized by four major steps: assembly of siRNA with the RNA-induced silencing complex (RISC), activation of the RISC, target recognition and target cleavage. These interactions may bias strand selection during siRNA-RISC assembly and activation, and contribute to the overall efficiency of RNAi. To identify siRNA-specific features likely to contribute to efficient processing at each step, we performed a systematic analysis of 180 siRNAs targeting the mRNA of two genes. Eight characteristics associated with siRNA functionality were identified: low G/C content, a bias towards low internal stability at the sense strand 3'-terminus, lack of inverted repeats, and sense strand base preferences (positions 3, 10, 13 and 19). Further analyses revealed that application of an algorithm incorporating all eight criteria significantly improves potent siRNA selection. This highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Nature Biotechnology 2004/2/1 Si2767 U92436 Vickers MMAC1 5728 GCGAGAGGCGGACGGGACCgc GGUCCCGUCCGCCUCUCGC -3.3 -3.4 -1.2 0 0 5 -48.7 19.1 9.8 0 II 78.9 34.4 0 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2768 U92436 Vickers MMAC1 5728 CCGGGCGCCUCGGAAGACCga GGUCUUCCGAGGCGCCCGG -3.3 -3.3 -2.7 0 -1 9 -48.3 18.1 3.1 -1 II 78.9 38.5 0 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2769 U92436 Vickers MMAC1 5728 AUGGCUGCAGCUUCCGAGAgg UCUCGGAAGCUGCAGCCAU -2.4 -1.1 -0.5 1 0 3 -43.1 56.6 -3.1 3 II 57.9 50.7 40 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2770 U92436 Vickers MMAC1 5728 CCCCGCGGCUGCUCACAGGcg CCUGUGAGCAGCCGCGGGG -3.3 -3.3 -8.1 1 -1 9 -48.7 26.2 -4.4 -1 II 78.9 32.8 25 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2771 U92436 Vickers MMAC1 5728 UCAGGAGAAGCCGAGGAAGag CUUCCUCGGCUUCUCCUGA -2.1 -2.4 -0.8 0 2 4 -42.1 36.4 -4.7 4 II 57.9 53.5 62 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2772 U92436 Vickers MMAC1 5728 CGGGAGGUGCCGCCGCCGCcg GCGGCGGCGGCACCUCCCG -3.4 -2.4 -1.2 0 0 11 -51.8 14.6 8.2 0 II 89.5 37.5 20 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2773 U92436 Vickers MMAC1 5728 CCCGGGUCCCUGGAUGUGCcg GCACAUCCAGGGACCCGGG -3.4 -3.3 -0.6 1 -1 6 -47.6 29.1 5.4 1 II 73.7 41.8 32 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2774 U92436 Vickers MMAC1 5728 UCCUCCGAACGGCUGCCUCcg GAGGCAGCCGUUCGGAGGA -2.4 -2.4 -1 0 3 4 -45.9 55.2 12.1 3 II 68.4 53.9 58 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2775 U92436 Vickers MMAC1 5728 UUCUCCUCAGCAGCCAGAGgc CUCUGGCUGCUGAGGAGAA -2.1 -0.9 -2.2 1 3 3 -42.8 63.1 -2.4 4 Ib 57.9 61.9 52 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2776 U92436 Vickers MMAC1 5728 CCGCUUGGCUCUGGACCGCag GCGGUCCAGAGCCAAGCGG -3.4 -3.3 -2.4 0 0 4 -46.6 26.1 6.1 0 II 73.7 36.5 31 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2777 U92436 Vickers MMAC1 5728 UUCUUCUGCAGGAUGGAAAug UUUCCAUCCUGCAGAAGAA -0.9 -0.9 0.7 2 0 2 -36.9 82 -4 8 II 42.1 58.8 27 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2778 U92436 Vickers MMAC1 5728 UGGAUAAAUAUAGGUCAAGuc CUUGACCUAUAUUUAUCCA -2.1 -2.1 3 -1 1 2 -31.9 67.6 0 7 Ia 31.6 62.5 48 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2779 U92436 Vickers MMAC1 5728 AUCAAUAUUGUUCCUGUAUac AUACAGGAACAAUAUUGAU -1.1 -1.1 0.4 1 0 2 -30.6 88.8 4.2 7 II 26.3 59.2 49 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2780 U92436 Vickers MMAC1 5728 AUUAAAUUUGGCGGUGUCAua UGACACCGCCAAAUUUAAU -2.1 -1.1 2 1 1 5 -33.5 70.1 -3.4 8 II 36.8 54.9 65 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2781 U92436 Vickers MMAC1 5728 UCAAGAUCUUCACAAAAGGgu CCUUUUGUGAAGAUCUUGA -3.3 -2.4 0.5 1 3 2 -33.3 66.5 0.1 6 Ia 36.8 67.5 73 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2782 U92436 Vickers MMAC1 5728 CAUUACACCAGUUCGUCCCuu GGGACGAACUGGUGUAAUG -3.3 -2.1 0.7 0 2 3 -38.5 78.6 11.1 6 II 52.6 61.8 75 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2783 U92436 Vickers MMAC1 5728 UUGUCUCUGGUCCUUACUUcc AAGUAAGGACCAGAGACAA -0.9 -0.9 1.8 1 2 2 -37 79.6 -1.6 5 II 42.1 63.4 75 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2784 U92436 Vickers MMAC1 5728 CACAUAGCGCCUCUGACUGgg CAGUCAGAGGCGCUAUGUG -2.1 -2.1 -0.5 0 1 5 -40.9 57.2 3.4 3 II 57.9 47.6 73 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2785 U92436 Vickers MMAC1 5728 GGAAUAUAUCUUCACCUUUag AAAGGUGAAGAUAUAUUCC -0.9 -3.3 0.2 1 -2 2 -31.8 71.5 1.5 5 II 31.6 45.6 9 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2786 U92436 Vickers MMAC1 5728 UGGAAGAACUCUACUUUGAua UCAAAGUAGAGUUCUUCCA -2.4 -2.1 1.2 1 -1 2 -34.8 71 -3 7 II 36.8 56.2 30 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2787 U92436 Vickers MMAC1 5728 AUGAAGAAUGUAUUUACCCaa GGGUAAAUACAUUCUUCAU -3.3 -1.1 -0.1 1 5 3 -31.6 80 12.4 6 Ia 31.6 78.2 70 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2788 U92436 Vickers MMAC1 5728 CGGUUGGCUUUGUCUUUAUuu AUAAAGACAAAGCCAACCG -1.1 -2.4 -1 -4 3 -34.5 64.5 -6 4 III 42.1 34.8 0 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2789 U92436 Vickers MMAC1 5728 CUGCUAGCCUCUGGAUUUGac CAAAUCCAGAGGCUAGCAG -2.1 -2.1 1.9 0 -1 3 -39.2 48 -1.3 4 II 52.6 41.4 44 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2790 U92436 Vickers MMAC1 5728 CUCUGGAUCAGAGUCAGUGgu CACUGACUCUGAUCCAGAG -2.1 -2.1 -3.5 0 1 2 -39.7 59.1 0.3 3 II 52.6 54.2 15 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2791 U92436 Vickers MMAC1 5728 UUAUUUUCAUGGUGUUUUAuc UAAAACACCAUGAAAAUAA -1.3 -0.9 1.1 0 0 2 -27.5 99.9 -3.8 9 II 21.1 62.7 58 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2792 U92436 Vickers MMAC1 5728 UUGUUCCUAUAACUGGUAAuc UUACCAGUUAUAGGAACAA -0.9 -0.9 -0.5 0 0 2 -32.6 87.9 3.3 7 II 31.6 52.9 40 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2793 U92436 Vickers MMAC1 5728 AGUGUCAAAACCCUGUGGAug UCCACAGGGUUUUGACACU -2.4 -2.1 0.2 1 2 3 -38.8 64.2 -3.7 6 II 47.4 48.3 45 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2794 U92436 Vickers MMAC1 5728 AACUGGAAUAAAACGGGAAag UUCCCGUUUUAUUCCAGUU -0.9 -0.9 3.8 1 0 4 -33.5 63 -4 6 II 36.8 49.4 38 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2795 U92436 Vickers MMAC1 5728 CACUUCAGUUGGUGACAGAac UCUGUCACCAACUGAAGUG -2.4 -2.1 0.2 -2 -3 2 -37.9 56.6 -5.8 4 II 47.4 33.9 25 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2796 U92436 Vickers MMAC1 5728 GUAGCAAAACCUUUCGGAAac UUCCGAAAGGUUUUGCUAC -0.9 -2.2 -3.6 0 0 3 -34.6 61.4 -0.8 2 II 42.1 35.9 32 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2797 U92436 Vickers MMAC1 5728 AAAUUAUUUCCUUUCUGAGca CUCAGAAAGGAAAUAAUUU -2.1 -0.9 1.2 2 5 2 -28.7 98.8 3 7 Ia 26.3 66 30 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2798 U92436 Vickers MMAC1 5728 GUAAAUAGCUGGAGAUGGUau ACCAUCUCCAGCUAUUUAC -2.2 -2.2 4.3 0 1 2 -36.3 54.6 -3.9 5 II 42.1 42.9 6 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2799 U92436 Vickers MMAC1 5728 CCAGAUUAAUAACUGUAGCau GCUACAGUUAUUAAUCUGG -3.4 -3.3 -1.9 0 1 2 -32.8 70.6 15.1 2 II 36.8 53.3 37 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2800 U92436 Vickers MMAC1 5728 ACCCCAAUACAGAUUCACUuc AGUGAAUCUGUAUUGGGGU -2.1 -2.2 0.3 2 1 4 -37.1 64.9 -1.9 3 II 42.1 49.2 39 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2801 U92436 Vickers MMAC1 5728 CAUUGUUGCUGUGUUUCUUac AAGAAACACAGCAACAAUG -0.9 -2.1 2.2 1 0 2 -32.7 80.4 -0.6 4 II 36.8 46.5 30 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2802 U92436 Vickers MMAC1 5728 AUGUUUCAAGCCCAUUCUUug AAGAAUGGGCUUGAAACAU -0.9 -1.1 0.9 1 1 4 -34.2 73.1 -6.3 5 II 36.8 54.2 40 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2803 J03132 Vickers ICAM-1 3383 GAGGAGCUCAGCGUCGACUgg AGUCGACGCUGAGCUCCUC -2.1 -2.4 0.7 1 0 3 -43.9 43.2 -1.3 2 III 63.2 42 0 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2804 J03132 Vickers ICAM-1 3383 GCUGAGGUUGCAACUCUGAgu UCAGAGUUGCAACCUCAGC -2.4 -3.4 -1.5 0 -2 2 -40.3 39.4 -6 3 III 52.6 33.4 1 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2805 J03132 Vickers ICAM-1 3383 CAGGCAGGAGCAACUCCUUuu AAGGAGUUGCUCCUGCCUG -0.9 -2.1 -4.7 -1 -2 3 -42.3 35.6 -10.9 0 III 57.9 38 -15 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2806 J03132 Vickers ICAM-1 3383 UGAAUAGCACAUUGGUUGGcu CCAACCAAUGUGCUAUUCA -3.3 -2.1 2.1 -1 3 2 -35.6 77.3 5.3 8 Ia 42.1 63.4 7 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2807 J03132 Vickers ICAM-1 3383 CCCACUGGCUGCCAAGAGGgg CCUCUUGGCAGCCAGUGGG -3.3 -3.3 -0.5 0 -1 3 -45.6 40.1 -2 1 II 68.4 38.7 18 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2808 J03132 Vickers ICAM-1 3383 CUCUCCUCACCAGCACCGUgg ACGGUGCUGGUGAGGAGAG -2.2 -2.1 1.3 0 -1 3 -44.2 45.8 -8.3 2 III 63.2 39.3 -20 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2809 J03132 Vickers ICAM-1 3383 AAGGUCUGGAGCUGGUAGGgg CCUACCAGCUCCAGACCUU -3.3 -0.9 2.6 2 3 2 -42.7 60.2 -2.4 5 Ib 57.9 59.2 45 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2810 J03132 Vickers ICAM-1 3383 CGUGUCCACCUCUAGGACCcg GGUCCUAGAGGUGGACACG -3.3 -2.4 -5.7 0 0 2 -43.4 49.1 3.1 0 II 63.2 47.8 10 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2811 J03132 Vickers ICAM-1 3383 CAGUGCCAGGUGGACCUGGgc CCAGGUCCACCUGGCACUG -3.3 -2.1 -7.5 0 0 3 -45.7 34 -2 1 II 68.4 44.4 21 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2812 J03132 Vickers ICAM-1 3383 CAGUAUUACUGCACACGUCag GACGUGUGCAGUAAUACUG -2.4 -2.1 -2.1 1 0 2 -36.4 63.7 3.2 3 II 47.4 53.8 30 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2813 J03132 Vickers ICAM-1 3383 CUCUGGCUUCGUCAGAAUCac GAUUCUGACGAAGCCAGAG -2.4 -2.1 -2.7 -1 -1 3 -38.8 60.7 10.8 1 II 52.6 47.2 -10 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2814 J03132 Vickers ICAM-1 3383 GUGGCCUUCAGCAGGAGCUgg AGCUCCUGCUGAAGGCCAC -2.1 -2.2 -2.1 1 0 4 -44.8 49.1 -8.9 1 III 63.2 44.6 10 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2815 J03132 Vickers ICAM-1 3383 AUACAGGACACGAAGCUCCcg GGAGCUUCGUGUCCUGUAU -3.3 -1.1 -1.5 3 4 2 -40 54.4 5.2 7 Ib 52.6 72.5 58 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2816 J03132 Vickers ICAM-1 3383 AUCCUUUAGACACUUGAGCuc GCUCAAGUGUCUAAAGGAU -3.4 -1.1 0.3 4 4 2 -36 78.5 9.8 6 Ia 42.1 69 40 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2817 J03132 Vickers ICAM-1 3383 CUCCUGGCCCGACAGAGGUag ACCUCUGUCGGGCCAGGAG -2.2 -2.1 -1.7 1 -1 6 -46.5 35.7 -3.6 1 III 68.4 39.7 5 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2818 J03132 Vickers ICAM-1 3383 CUACCACAGUGAUGAUGACaa GUCAUCAUCACUGUGGUAG -2.2 -2.1 -1.3 0 1 2 -37.5 48.3 5.4 1 II 47.4 36.4 35 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2819 J03132 Vickers ICAM-1 3383 UGUGUGUUCGGUUUCAUGGgg CCAUGAAACCGAACACACA -3.3 -2.1 2.1 2 4 3 -36.9 87.5 5.4 7 Ib 47.4 73.5 59 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2820 J03132 Vickers ICAM-1 3383 GAGGCGUGGCUUGUGUGUUcg AACACACAAGCCACGCCUC -0.9 -2.4 1.3 2 0 4 -41.4 46.7 1.4 1 III 57.9 36.9 1 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2821 J03132 Vickers ICAM-1 3383 CUGUCCCGGGAUAGGUUCAgg UGAACCUAUCCCGGGACAG -2.1 -2.1 -1.7 -1 -3 6 -42.2 50.9 -3 1 III 57.9 34.5 20 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2822 J03132 Vickers ICAM-1 3383 GAGGAAGAGGCCCUGUCCCgg GGGACAGGGCCUCUUCCUC -3.3 -2.4 -3.6 1 3 5 -46.4 37 10.1 1 II 68.4 47.3 52 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2823 J03132 Vickers ICAM-1 3383 CCACUCUGUUCAGUGUGGCac GCCACACUGAACAGAGUGG -3.4 -3.3 -3.5 1 2 3 -41.3 48.3 5.4 1 II 57.9 45.1 21 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2824 J03132 Vickers ICAM-1 3383 CUGACUGAGGACAAUGCCCug GGGCAUUGUCCUCAGUCAG -3.3 -2.1 -4.1 0 1 4 -41.6 53.9 2.8 1 II 57.9 59.3 62 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2825 J03132 Vickers ICAM-1 3383 AGGUGUGCAGGUACCAUGGcc CCAUGGUACCUGCACACCU -3.3 -2.1 -1.4 1 2 2 -42.5 59.1 0.4 3 II 57.9 57.3 75 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2826 J03132 Vickers ICAM-1 3383 CUCUCAUCAGGCUAGACUUua AAGUCUAGCCUGAUGAGAG -0.9 -2.1 -0.9 0 -2 3 -38.6 66.7 -8.3 3 II 47.4 44.7 50 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2827 J03132 Vickers ICAM-1 3383 CAGUUGUAUGUCCUCAUGGug CCAUGAGGACAUACAACUG -3.3 -2.1 -0.3 0 1 2 -37.1 71 0.4 5 II 47.4 60.7 58 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2828 J03132 Vickers ICAM-1 3383 GGCCUCAGCAUACCCAAUAgg UAUUGGGUAUGCUGAGGCC -1.3 -3.3 -0.8 2 -4 4 -40.8 47.3 -1.4 3 III 52.6 34 43 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2829 J03132 Vickers ICAM-1 3383 UGCUACACAUGUCUAUGGAgg UCCAUAGACAUGUGUAGCA -2.4 -2.1 -0.9 0 1 2 -37.6 74.3 6.7 6 II 42.1 48 63 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2830 J03132 Vickers ICAM-1 3383 CCCAAGCUGGCAUCCGUCAgg UGACGGAUGCCAGCUUGGG -2.1 -3.3 -1 0 -4 3 -44 38 -5.4 1 III 63.2 31.9 29 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2831 J03132 Vickers ICAM-1 3383 GUGCCCAAGCUGGCAUCCGuc CGGAUGCCAGCUUGGGCAC -2.4 -2.2 -5.1 2 2 4 -45 35.2 0 0 II 68.4 45.4 24 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2832 J03132 Vickers ICAM-1 3383 AGUGCCCAAGCUGGCAUCCgu GGAUGCCAGCUUGGGCACU -3.3 -2.1 -5.1 0 3 4 -44.7 47.7 8.1 2 II 63.2 50.5 40 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2833 J03132 Vickers ICAM-1 3383 CUCCGUGAGGCCAGAGACCua GGUCUCUGGCCUCACGGAG -3.3 -2.1 -5.1 0 0 4 -45.6 29.3 -1.9 0 II 68.4 46.8 7 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2834 J03132 Vickers ICAM-1 3383 AGGCACUCUCCUGCAGUGUac ACACUGCAGGAGAGUGCCU -2.2 -2.1 -2.1 3 0 3 -43.7 49 -0.6 3 II 57.9 44.6 0 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2835 J03132 Vickers ICAM-1 3383 AAAGGCAGGUUGGCCAAUGag CAUUGGCCAACCUGCCUUU -2.1 -0.9 -3.3 2 3 4 -39.5 47 0 4 Ib 52.6 59.7 28 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2836 J03132 Vickers ICAM-1 3383 GUAAUCUCUGAACCUGUGAac UCACAGGUUCAGAGAUUAC -2.4 -2.2 1.7 1 -1 2 -36.3 70.8 1 6 II 42.1 46.9 34 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2837 J03132 Vickers ICAM-1 3383 UCCAGACAUGACCGCUGAGug CUCAGCGGUCAUGUCUGGA -2.1 -2.4 -1.1 -1 2 4 -42.2 45.4 2.4 2 II 57.9 45.7 33 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2838 J03132 Vickers ICAM-1 3383 UGGAGCUGCAAUAGUGCAAgc UUGCACUAUUGCAGCUCCA -0.9 -2.1 -2.8 1 -1 2 -39.1 62.5 -1 5 II 47.4 49.2 5 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2839 J03132 Vickers ICAM-1 3383 ACACAUACACACACACACAca UGUGUGUGUGUGUAUGUGU -2.1 -2.2 3.8 2 0 1 -36.8 55.7 -3.7 5 II 42.1 52.5 7 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2840 J03132 Vickers ICAM-1 3383 CUGAGGUGGGAGGAUCACUug AGUGAUCCUCCCACCUCAG -2.1 -2.1 -0.9 1 -2 3 -43 42.7 -3.7 2 III 57.9 47.3 45 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2841 J03132 Vickers ICAM-1 3383 GUGUGGUGUUGUGAGCCUAug UAGGCUCACAACACCACAC -1.3 -2.2 0.1 1 -2 3 -40.3 47.3 -0.7 3 III 52.6 35.2 41 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2842 J03132 Vickers ICAM-1 3383 UAACACAAAGGAAGUCUGGgc CCAGACUUCCUUUGUGUUA -3.3 -1.3 0.4 0 4 2 -35.5 63.3 0.1 8 Ia 42.1 69.5 48 RT-PCR T24 200nM 16h Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. 12500975 2003 RNA interference can be considered as an antisense mechanism of action that utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have performed a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligonucleotides designed to work by an RNase H-dependent mechanism in human cells. The potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were evaluated and found to be comparable. Effects of base mismatches on activity were determined to be position-dependent for both siRNA oligonucleotides and RNase H-dependent oligonucleotides. In addition, we determined that the activity of both siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the secondary structure of the target mRNA. To determine whether positions on target RNA identified as being susceptible for RNase H-mediated degradation would be coincident with siRNA target sites, we evaluated the effectiveness of siRNAs designed to bind the same position on the target mRNA as RNase H-dependent oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to bind to RNA from four distinct human genes revealed that, in general, activity correlated with the activity to RNase H-dependent oligonucleotides designed to the same site, although some exceptions were noted. The one major difference between the two strategies is that RNase H-dependent oligonucleotides were determined to be active when directed against targets in the pre-mRNA, whereas siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase H-dependent antisense strategies are both valid strategies for evaluating function of genes in cell-based assays. Journal of Biological Chemistry 2003/2/1 Si2843 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUCGCCCUUGCUCACCAU AUGGUGAGCAAGGGCGAGG -1.1 -3.30 -1.10 0.00 -2.00 5.00 -44 37.90 -8.30 -1.00 III 63.20 24.10 54.75 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 3-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2844 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCUCGCCCUUGCUCACCA UGGUGAGCAAGGGCGAGGA -2.1 -2.40 -1.10 1.00 1.00 5.00 -45.3 52.40 1.00 2.00 II 63.20 48.60 77.71 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 4-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2845 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCCUCGCCCUUGCUCACC GGUGAGCAAGGGCGAGGAG -3.3 -2.10 -1.10 1.00 0.00 5.00 -45.3 47.10 8.40 1.00 II 68.40 51.20 60.16 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 5-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2846 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUCCUCGCCCUUGCUCAC GUGAGCAAGGGCGAGGAGC -2.2 -3.40 -1.10 1.00 1.00 5.00 -45.4 42.90 8.10 -1.00 II 68.40 29.60 38.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 6-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2847 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUCCUCGCCCUUGCUCA UGAGCAAGGGCGAGGAGCU -2.1 -2.10 -2.00 3.00 0.00 5.00 -45.3 61.00 -6.10 3.00 II 63.20 44.50 65.08 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 7-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2848 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCUCCUCGCCCUUGCUC GAGCAAGGGCGAGGAGCUG -2.4 -2.10 -2.70 1.00 1.00 5.00 -45.3 49.50 5.40 0.00 II 68.40 45.60 44.55 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 8-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2849 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACAGCUCCUCGCCCUUGCU AGCAAGGGCGAGGAGCUGU -2.1 -2.20 -2.70 1.00 2.00 5.00 -45.1 48.50 -3.90 1.00 II 63.20 44.70 53.61 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 9-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2850 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AACAGCUCCUCGCCCUUGC GCAAGGGCGAGGAGCUGUU -3.4 -0.90 -2.70 3.00 3.00 5.00 -43.9 61.40 7.50 4.00 Ib 63.20 59.30 75.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2851 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAACAGCUCCUCGCCCUUG CAAGGGCGAGGAGCUGUUC -2.1 -2.40 -2.70 2.00 1.00 5.00 -42.9 38.70 0.40 2.00 II 63.20 45.00 42.30 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2852 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAACAGCUCCUCGCCCUU AAGGGCGAGGAGCUGUUCA -0.9 -2.10 -2.90 -1.00 1.00 5.00 -42.9 50.00 -0.90 4.00 II 57.90 50.60 56.28 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2853 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGAACAGCUCCUCGCCCU AGGGCGAGGAGCUGUUCAC -2.1 -2.20 -2.90 1.00 0.00 5.00 -44.2 47.70 -6.00 2.00 II 63.20 44.40 73.97 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2854 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGAACAGCUCCUCGCCC GGGCGAGGAGCUGUUCACC -3.3 -3.30 -2.70 1.00 3.00 5.00 -45.4 35.30 12.50 0.00 II 68.40 41.10 52.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2855 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGUGAACAGCUCCUCGCC GGCGAGGAGCUGUUCACCG -3.3 -2.40 -2.30 -1.00 0.00 4.00 -44.5 43.20 8.50 0.00 II 68.40 43.90 31.59 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2856 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGGUGAACAGCUCCUCGC GCGAGGAGCUGUUCACCGG -3.4 -3.30 -1.20 0.00 0.00 4.00 -44.5 45.40 3.10 1.00 II 68.40 50.40 66.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2857 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCGGUGAACAGCUCCUCG CGAGGAGCUGUUCACCGGG -2.4 -3.30 -0.40 -1.00 0.00 5.00 -44.4 41.90 5.00 1.00 II 68.40 43.80 39.28 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2858 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCCGGUGAACAGCUCCUC GAGGAGCUGUUCACCGGGG -2.4 -3.30 -0.40 1.00 -1.00 6.00 -45.3 30.30 3.10 1.00 II 68.40 40.40 12.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2859 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACCCCGGUGAACAGCUCCU AGGAGCUGUUCACCGGGGU -2.1 -2.20 -0.40 2.00 1.00 6.00 -45.1 39.80 -6.60 3.00 II 63.20 45.80 50.06 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2860 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACCCCGGUGAACAGCUCC GGAGCUGUUCACCGGGGUG -3.3 -2.10 -1.70 0.00 0.00 6.00 -45.1 44.00 10.10 1.00 II 68.40 49.80 66.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2861 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCACCCCGGUGAACAGCUC GAGCUGUUCACCGGGGUGG -2.4 -3.30 -3.00 1.00 0.00 6.00 -45.1 28.90 2.80 -1.00 II 68.40 34.60 51.08 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2862 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACCACCCCGGUGAACAGCU AGCUGUUCACCGGGGUGGU -2.1 -2.20 -3.40 2.00 1.00 6.00 -44.9 40.50 -6.60 1.00 II 63.20 46.00 60.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2863 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACCACCCCGGUGAACAGC GCUGUUCACCGGGGUGGUG -3.4 -2.10 -3.40 1.00 0.00 6.00 -44.9 38.20 11.10 0.00 II 68.40 42.60 48.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2864 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCACCACCCCGGUGAACAG CUGUUCACCGGGGUGGUGC -2.1 -3.40 -3.60 1.00 1.00 6.00 -44.9 30.00 0.00 -1.00 II 68.40 25.60 33.58 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2865 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCACCACCCCGGUGAACA UGUUCACCGGGGUGGUGCC -2.1 -3.30 -3.60 1.00 -2.00 6.00 -46.1 40.70 -3.80 0.00 III 68.40 30.50 54.98 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2866 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCACCACCCCGGUGAAC GUUCACCGGGGUGGUGCCC -2.2 -3.30 -3.60 1.00 -1.00 6.00 -47.3 20.50 5.40 -1.00 II 73.70 22.90 29.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2867 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGGCACCACCCCGGUGAA UUCACCGGGGUGGUGCCCA -0.9 -2.10 -4.90 -1.00 -1.00 6.00 -47.2 31.50 -6.10 1.00 II 68.40 29.30 25.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2868 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGGGCACCACCCCGGUGA UCACCGGGGUGGUGCCCAU -2.4 -1.10 -4.90 2.00 0.00 6.00 -47.4 44.30 -6.10 4.00 II 68.40 50.50 44.92 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2869 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGGGCACCACCCCGGUG CACCGGGGUGGUGCCCAUC -2.1 -2.40 -4.90 1.00 2.00 6.00 -47.4 32.70 2.40 0.00 II 73.70 38.70 30.48 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2870 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGAUGGGCACCACCCCGGU ACCGGGGUGGUGCCCAUCC -2.2 -3.30 -5.90 0.00 0.00 6.00 -48.6 24.30 -3.90 1.00 III 73.70 30.40 28.39 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2871 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGAUGGGCACCACCCCGG CCGGGGUGGUGCCCAUCCU -3.3 -2.10 -7.80 2.00 3.00 6.00 -48.5 37.60 -7.30 4.00 II 73.70 58.20 47.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2872 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGAUGGGCACCACCCCG CGGGGUGGUGCCCAUCCUG -2.4 -2.10 -9.40 0.00 1.00 5.00 -47.3 32.90 3.10 1.00 II 73.70 51.70 32.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2873 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAGGAUGGGCACCACCCC GGGGUGGUGCCCAUCCUGG -3.3 -3.30 -8.20 1.00 1.00 4.00 -48.2 23.40 5.50 0.00 II 73.70 45.40 17.03 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2874 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACCAGGAUGGGCACCACCC GGGUGGUGCCCAUCCUGGU -3.3 -2.20 -7.10 2.00 3.00 4.00 -47.1 42.10 2.50 2.00 II 68.40 59.90 61.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2875 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GACCAGGAUGGGCACCACC GGUGGUGCCCAUCCUGGUC -3.3 -2.40 -3.40 1.00 1.00 4.00 -46.2 34.80 12.50 1.00 II 68.40 47.50 42.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2876 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGACCAGGAUGGGCACCAC GUGGUGCCCAUCCUGGUCG -2.2 -2.40 -1.00 0.00 0.00 4.00 -45.3 27.20 5.40 0.00 II 68.40 31.50 27.27 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2877 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGACCAGGAUGGGCACCA UGGUGCCCAUCCUGGUCGA -2.1 -2.40 -1.00 0.00 0.00 4.00 -45.5 40.40 -3.80 4.00 II 63.20 52.60 52.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2878 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGACCAGGAUGGGCACC GGUGCCCAUCCUGGUCGAG -3.3 -2.10 -1.00 -1.00 0.00 4.00 -45.5 35.20 13.40 0.00 II 68.40 42.80 30.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2879 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUCGACCAGGAUGGGCAC GUGCCCAUCCUGGUCGAGC -2.2 -3.40 -1.00 0.00 1.00 4.00 -45.6 28.10 7.40 -1.00 II 68.40 25.20 17.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2880 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUCGACCAGGAUGGGCA UGCCCAUCCUGGUCGAGCU -2.1 -2.10 -1.00 2.00 1.00 4.00 -45.5 52.60 -4.00 3.00 II 63.20 46.70 54.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2881 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCUCGACCAGGAUGGGC GCCCAUCCUGGUCGAGCUG -3.4 -2.10 -0.80 1.00 1.00 4.00 -45.5 38.60 7.70 2.00 II 68.40 46.00 39.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2882 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAGCUCGACCAGGAUGGG CCCAUCCUGGUCGAGCUGG -3.3 -3.30 -0.80 -2.00 1.00 3.00 -45.4 23.10 -4.40 0.00 II 68.40 31.70 33.97 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2883 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCAGCUCGACCAGGAUGG CCAUCCUGGUCGAGCUGGA -3.3 -2.40 -1.90 1.00 2.00 2.00 -44.5 52.50 -7.30 5.00 II 63.20 61.20 64.10 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2884 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCCAGCUCGACCAGGAUG CAUCCUGGUCGAGCUGGAC -2.1 -2.20 -1.90 2.00 0.00 2.00 -43.4 42.60 5.10 0.00 II 63.20 41.30 59.28 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2885 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCCAGCUCGACCAGGAU AUCCUGGUCGAGCUGGACG -1.1 -2.40 -2.50 0.00 -2.00 2.00 -43.7 34.60 -3.60 0.00 III 63.20 24.40 31.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2886 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUCCAGCUCGACCAGGA UCCUGGUCGAGCUGGACGG -2.4 -3.30 -2.50 0.00 -3.00 3.00 -45.9 34.60 -10.70 0.00 III 68.40 29.90 48.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2887 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUCCAGCUCGACCAGG CCUGGUCGAGCUGGACGGC -3.3 -3.40 -2.50 1.00 0.00 4.00 -46.9 22.70 -2.40 -1.00 II 73.70 33.30 33.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2888 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCCGUCCAGCUCGACCAG CUGGUCGAGCUGGACGGCG -2.1 -2.40 -3.30 -1.00 -1.00 5.00 -46 25.90 1.10 -2.00 II 73.70 26.00 30.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2889 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGCCGUCCAGCUCGACCA UGGUCGAGCUGGACGGCGA -2.1 -2.40 -3.30 3.00 0.00 5.00 -46.3 52.80 -6.10 3.00 II 68.40 56.50 76.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2890 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGCCGUCCAGCUCGACC GGUCGAGCUGGACGGCGAC -3.3 -2.20 -3.30 1.00 2.00 5.00 -46.4 49.10 14.40 0.00 II 73.70 47.80 71.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2891 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCGCCGUCCAGCUCGAC GUCGAGCUGGACGGCGACG -2.2 -2.40 -3.50 0.00 0.00 5.00 -45.5 24.30 3.10 -1.00 II 73.70 28.70 24.97 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2892 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGUCGCCGUCCAGCUCGA UCGAGCUGGACGGCGACGU -2.4 -2.20 -3.00 1.00 0.00 5.00 -45.5 28.80 -11.00 1.00 II 68.40 31.40 28.91 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2893 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UACGUCGCCGUCCAGCUCG CGAGCUGGACGGCGACGUA -2.4 -1.30 -3.50 1.00 3.00 5.00 -44.4 53.70 0.10 5.00 II 68.40 70.40 52.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2894 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUACGUCGCCGUCCAGCUC GAGCUGGACGGCGACGUAA -2.4 -0.90 -3.50 2.00 4.00 5.00 -42.9 55.40 12.80 3.00 Ib 63.20 63.90 59.28 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2895 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUUACGUCGCCGUCCAGCU AGCUGGACGGCGACGUAAA -2.1 -0.90 -3.50 2.00 3.00 5.00 -41.4 67.90 -6.30 5.00 II 57.90 67.60 44.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2896 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUUACGUCGCCGUCCAGC GCUGGACGGCGACGUAAAC -3.4 -2.20 -3.50 1.00 3.00 5.00 -41.5 53.90 7.70 3.00 II 63.20 51.50 57.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2897 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUUUACGUCGCCGUCCAG CUGGACGGCGACGUAAACG -2.1 -2.40 -3.50 -2.00 0.00 5.00 -40.5 42.10 -2.00 1.00 II 63.20 29.40 37.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2898 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUUUACGUCGCCGUCCA UGGACGGCGACGUAAACGG -2.1 -3.30 -3.50 0.00 -3.00 5.00 -41.7 45.50 -5.70 1.00 II 63.20 34.60 32.38 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2899 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUUUACGUCGCCGUCC GGACGGCGACGUAAACGGC -3.3 -3.40 -3.50 2.00 0.00 5.00 -43 43.90 5.10 1.00 II 68.40 48.70 35.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2900 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCCGUUUACGUCGCCGUC GACGGCGACGUAAACGGCC -2.4 -3.30 -3.50 1.00 0.00 5.00 -43 42.30 12.80 -1.00 II 68.40 34.20 44.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2901 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGCCGUUUACGUCGCCGU ACGGCGACGUAAACGGCCA -2.2 -2.10 -3.80 2.00 1.00 5.00 -42.7 57.00 -6.30 3.00 II 63.20 57.70 68.59 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2902 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGCCGUUUACGUCGCCG CGGCGACGUAAACGGCCAC -2.4 -2.20 -3.80 0.00 3.00 5.00 -42.7 45.80 2.30 0.00 II 68.40 48.10 70.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2903 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUGGCCGUUUACGUCGCC GGCGACGUAAACGGCCACA -3.3 -2.10 -3.50 -1.00 4.00 5.00 -42.4 42.00 9.80 2.00 II 63.20 54.80 44.03 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2904 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUGGCCGUUUACGUCGC GCGACGUAAACGGCCACAA -3.4 -0.90 -0.50 1.00 4.00 5.00 -40 58.60 7.80 4.00 II 57.90 65.80 49.96 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2905 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGUGGCCGUUUACGUCG CGACGUAAACGGCCACAAG -2.4 -2.10 -0.50 0.00 1.00 5.00 -38.7 59.80 1.00 4.00 II 57.90 61.20 57.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2906 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUUGUGGCCGUUUACGUC GACGUAAACGGCCACAAGU -2.4 -2.20 -0.50 2.00 4.00 5.00 -38.5 67.50 12.80 5.00 Ib 52.60 54.90 53.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2907 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AACUUGUGGCCGUUUACGU ACGUAAACGGCCACAAGUU -2.2 -0.90 -0.50 3.00 3.00 5.00 -37 71.60 -4.00 6.00 II 47.40 55.80 53.84 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2908 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAACUUGUGGCCGUUUACG CGUAAACGGCCACAAGUUC -2.4 -2.40 0.00 2.00 3.00 5.00 -37.2 59.00 -2.40 4.00 II 52.60 53.90 68.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2909 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAACUUGUGGCCGUUUAC GUAAACGGCCACAAGUUCA -2.2 -2.10 0.40 0.00 2.00 5.00 -36.9 74.60 7.50 7.00 Ia 47.40 61.80 82.92 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2910 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGAACUUGUGGCCGUUUA UAAACGGCCACAAGUUCAG -1.3 -2.10 0.40 1.00 -4.00 5.00 -36.8 64.40 -0.70 5.00 II 47.40 39.00 55.22 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2911 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUGAACUUGUGGCCGUUU AAACGGCCACAAGUUCAGC -0.9 -3.40 0.40 0.00 -2.00 5.00 -38.9 40.10 -1.30 3.00 III 52.60 30.10 41.81 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2912 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCUGAACUUGUGGCCGUU AACGGCCACAAGUUCAGCG -0.9 -2.40 0.40 -2.00 -3.00 5.00 -40.4 37.80 -3.00 1.00 III 57.90 26.00 42.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2913 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGCUGAACUUGUGGCCGU ACGGCCACAAGUUCAGCGU -2.2 -2.20 0.40 2.00 1.00 5.00 -41.7 40.40 -4.00 3.00 II 57.90 44.50 68.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2914 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACGCUGAACUUGUGGCCG CGGCCACAAGUUCAGCGUG -2.4 -2.10 0.30 -1.00 2.00 5.00 -41.6 50.00 3.40 1.00 II 63.20 50.70 63.77 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2915 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACACGCUGAACUUGUGGCC GGCCACAAGUUCAGCGUGU -3.3 -2.20 -0.30 2.00 4.00 4.00 -41.4 54.90 8.10 4.00 II 57.90 56.40 59.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2916 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GACACGCUGAACUUGUGGC GCCACAAGUUCAGCGUGUC -3.4 -2.40 -0.30 1.00 3.00 3.00 -40.5 65.40 9.70 2.00 II 57.90 47.60 74.71 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2917 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGACACGCUGAACUUGUGG CCACAAGUUCAGCGUGUCC -3.3 -3.30 -0.30 1.00 2.00 3.00 -40.4 49.50 9.70 3.00 II 57.90 43.30 84.19 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2918 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGACACGCUGAACUUGUG CACAAGUUCAGCGUGUCCG -2.1 -2.40 0.00 0.00 -1.00 3.00 -39.5 44.00 -4.60 0.00 II 57.90 34.30 56.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2919 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGGACACGCUGAACUUGU ACAAGUUCAGCGUGUCCGG -2.2 -3.30 0.70 0.00 -3.00 4.00 -40.7 37.10 -5.90 2.00 III 57.90 39.20 53.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2920 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGGACACGCUGAACUUG CAAGUUCAGCGUGUCCGGC -2.1 -3.40 0.70 1.00 -1.00 5.00 -41.9 28.60 0.70 0.00 II 63.20 30.40 57.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2921 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCCGGACACGCUGAACUU AAGUUCAGCGUGUCCGGCG -0.9 -2.40 -1.00 -1.00 -3.00 6.00 -42.2 31.30 -8.30 -1.00 III 63.20 28.20 40.43 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2922 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGCCGGACACGCUGAACU AGUUCAGCGUGUCCGGCGA -2.1 -2.40 -1.00 2.00 1.00 6.00 -43.7 50.70 -1.60 3.00 II 63.20 57.30 73.34 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2923 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGCCGGACACGCUGAAC GUUCAGCGUGUCCGGCGAG -2.2 -2.10 -1.00 -1.00 -1.00 6.00 -43.7 40.40 5.40 0.00 II 68.40 38.30 49.53 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2924 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUCGCCGGACACGCUGAA UUCAGCGUGUCCGGCGAGG -0.9 -3.30 -1.00 0.00 -3.00 6.00 -44.8 21.10 -5.70 0.00 III 68.40 16.30 39.52 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2925 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCUCGCCGGACACGCUGA UCAGCGUGUCCGGCGAGGG -2.4 -3.30 -1.30 0.00 -4.00 6.00 -47.2 31.10 -8.40 0.00 III 73.70 25.50 34.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2926 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCCUCGCCGGACACGCUG CAGCGUGUCCGGCGAGGGC -2.1 -3.40 -3.90 2.00 0.00 6.00 -48.2 26.20 2.40 0.00 II 78.90 34.40 49.31 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2927 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCCCUCGCCGGACACGCU AGCGUGUCCGGCGAGGGCG -2.1 -2.40 -5.60 1.00 -2.00 6.00 -48.5 25.40 -8.60 -2.00 III 78.90 27.90 49.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2928 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGCCCUCGCCGGACACGC GCGUGUCCGGCGAGGGCGA -3.4 -2.40 -5.80 3.00 3.00 6.00 -48.8 35.70 5.10 2.00 II 78.90 58.30 38.91 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2929 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGCCCUCGCCGGACACG CGUGUCCGGCGAGGGCGAG -2.4 -2.10 -5.80 -1.00 0.00 6.00 -47.5 26.80 -6.70 -1.00 II 78.90 39.40 39.16 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2930 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUCGCCCUCGCCGGACAC GUGUCCGGCGAGGGCGAGG -2.2 -3.30 -5.80 -1.00 0.00 6.00 -48.4 24.80 5.50 -1.00 II 78.90 27.70 40.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2931 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCUCGCCCUCGCCGGACA UGUCCGGCGAGGGCGAGGG -2.1 -3.30 -5.60 0.00 -4.00 6.00 -49.5 28.20 -5.70 -1.00 III 78.90 22.30 51.32 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2932 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCCUCGCCCUCGCCGGAC GUCCGGCGAGGGCGAGGGC -2.2 -3.40 -5.60 2.00 0.00 6.00 -50.8 20.30 5.10 0.00 II 84.20 29.30 52.80 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2933 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCCCUCGCCCUCGCCGGA UCCGGCGAGGGCGAGGGCG -2.4 -2.40 -1.40 0.00 -3.00 6.00 -51 18.70 -2.70 -2.00 III 84.20 17.50 44.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2934 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGCCCUCGCCCUCGCCGG CCGGCGAGGGCGAGGGCGA -3.3 -2.40 -1.20 3.00 3.00 6.00 -51 39.30 -4.70 2.00 II 84.20 55.60 34.77 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2935 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUCGCCCUCGCCCUCGCCG CGGCGAGGGCGAGGGCGAU -2.4 -1.10 -1.10 2.00 5.00 5.00 -48.8 45.40 0.00 1.00 II 78.90 56.40 30.26 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2936 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAUCGCCCUCGCCCUCGCC GGCGAGGGCGAGGGCGAUG -3.3 -2.10 -1.10 0.00 2.00 5.00 -48.5 36.80 5.50 0.00 II 78.90 43.50 38.74 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2937 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCAUCGCCCUCGCCCUCGC GCGAGGGCGAGGGCGAUGC -3.4 -3.40 -1.10 1.00 2.00 5.00 -48.6 33.20 7.50 0.00 II 78.90 35.30 33.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2938 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCAUCGCCCUCGCCCUCG CGAGGGCGAGGGCGAUGCC -2.4 -3.30 -2.00 1.00 0.00 5.00 -48.5 34.40 -2.40 2.00 II 78.90 41.90 29.27 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2939 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGCAUCGCCCUCGCCCUC GAGGGCGAGGGCGAUGCCA -2.4 -2.10 -3.70 1.00 2.00 5.00 -48.2 38.10 13.20 2.00 II 73.70 51.90 30.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2940 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGCAUCGCCCUCGCCCU AGGGCGAGGGCGAUGCCAC -2.1 -2.20 -3.70 2.00 0.00 5.00 -48 37.90 -8.70 0.00 III 73.70 40.30 39.74 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2941 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGGCAUCGCCCUCGCCC GGGCGAGGGCGAUGCCACC -3.3 -3.30 -3.70 1.00 3.00 5.00 -49.2 37.90 7.40 0.00 II 78.90 46.30 16.30 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2942 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGUGGCAUCGCCCUCGCC GGCGAGGGCGAUGCCACCU -3.3 -2.10 -3.70 1.00 3.00 5.00 -48 38.10 7.50 1.00 II 73.70 48.40 39.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2943 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGGUGGCAUCGCCCUCGC GCGAGGGCGAUGCCACCUA -3.4 -1.30 -2.70 0.00 4.00 5.00 -46 49.10 7.50 4.00 II 68.40 64.80 28.52 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2944 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGGUGGCAUCGCCCUCG CGAGGGCGAUGCCACCUAC -2.4 -2.20 -2.70 1.00 2.00 5.00 -44.8 39.50 -2.40 3.00 II 68.40 56.90 36.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2945 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUAGGUGGCAUCGCCCUC GAGGGCGAUGCCACCUACG -2.4 -2.40 -2.70 0.00 0.00 5.00 -44.8 40.40 13.10 1.00 II 68.40 41.80 32.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2946 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUAGGUGGCAUCGCCCU AGGGCGAUGCCACCUACGG -2.1 -3.30 -2.70 0.00 -2.00 5.00 -45.7 33.70 -5.60 1.00 III 68.40 38.10 24.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2947 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUAGGUGGCAUCGCCC GGGCGAUGCCACCUACGGC -3.3 -3.40 -2.80 0.00 2.00 5.00 -47 32.10 4.80 0.00 II 73.70 42.20 32.13 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2948 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCGUAGGUGGCAUCGCC GGCGAUGCCACCUACGGCA -3.3 -2.10 -4.70 2.00 3.00 4.00 -45.8 44.80 9.80 2.00 II 68.40 58.50 48.71 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2949 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGCCGUAGGUGGCAUCGC GCGAUGCCACCUACGGCAA -3.4 -0.90 -5.50 3.00 4.00 4.00 -43.4 48.60 7.40 3.00 II 63.20 67.70 39.58 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2950 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGCCGUAGGUGGCAUCG CGAUGCCACCUACGGCAAG -2.4 -2.10 -5.50 -2.00 1.00 4.00 -42.1 52.00 1.00 2.00 II 63.20 50.00 54.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2951 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUUGCCGUAGGUGGCAUC GAUGCCACCUACGGCAAGC -2.4 -3.40 -5.50 -1.00 0.00 4.00 -43.1 45.50 7.40 1.00 II 63.20 33.70 31.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2952 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUUGCCGUAGGUGGCAU AUGCCACCUACGGCAAGCU -1.1 -2.10 -5.50 2.00 1.00 4.00 -42.8 49.00 0.70 2.00 II 57.90 34.30 46.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2953 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCUUGCCGUAGGUGGCA UGCCACCUACGGCAAGCUG -2.1 -2.10 -5.20 0.00 -2.00 4.00 -43.8 32.00 -5.80 1.00 III 63.20 37.60 19.27 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2954 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCAGCUUGCCGUAGGUGGC GCCACCUACGGCAAGCUGA -3.4 -2.40 -4.50 1.00 4.00 4.00 -44.1 55.80 7.80 3.00 Ib 63.20 61.70 45.26 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2955 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCAGCUUGCCGUAGGUGG CCACCUACGGCAAGCUGAC -3.3 -2.20 -1.90 2.00 1.00 4.00 -42.9 54.70 -2.40 2.00 II 63.20 47.20 55.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2956 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCAGCUUGCCGUAGGUG CACCUACGGCAAGCUGACC -2.1 -3.30 -1.90 1.00 2.00 4.00 -42.9 35.20 0.30 0.00 II 63.20 33.90 34.74 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2957 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUCAGCUUGCCGUAGGU ACCUACGGCAAGCUGACCC -2.2 -3.30 -1.90 -1.00 -1.00 4.00 -44.1 37.60 -3.90 0.00 III 63.20 23.80 39.10 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2958 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGGUCAGCUUGCCGUAGG CCUACGGCAAGCUGACCCU -3.3 -2.10 -1.90 2.00 2.00 4.00 -44 48.20 2.40 2.00 II 63.20 52.30 67.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2959 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGGUCAGCUUGCCGUAG CUACGGCAAGCUGACCCUG -2.1 -2.10 -1.90 0.00 -1.00 4.00 -42.8 39.80 1.00 0.00 II 63.20 40.70 30.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2960 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCAGGGUCAGCUUGCCGUA UACGGCAAGCUGACCCUGA -1.3 -2.40 -1.90 0.00 0.00 4.00 -43.1 44.80 -3.10 3.00 II 57.90 48.50 48.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2961 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCAGGGUCAGCUUGCCGU ACGGCAAGCUGACCCUGAA -2.2 -0.90 -1.90 1.00 3.00 4.00 -42.7 66.70 -4.00 5.00 II 57.90 65.70 74.98 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2962 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUCAGGGUCAGCUUGCCG CGGCAAGCUGACCCUGAAG -2.4 -2.10 -1.40 0.00 3.00 4.00 -42.6 48.30 7.70 2.00 II 63.20 51.90 64.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2963 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUUCAGGGUCAGCUUGCC GGCAAGCUGACCCUGAAGU -3.3 -2.20 -0.20 2.00 4.00 3.00 -42.4 48.30 5.10 4.00 Ib 57.90 49.50 62.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2964 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AACUUCAGGGUCAGCUUGC GCAAGCUGACCCUGAAGUU -3.4 -0.90 -0.80 1.00 3.00 3.00 -40 60.40 2.50 7.00 Ia 52.60 61.40 69.63 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2965 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAACUUCAGGGUCAGCUUG CAAGCUGACCCUGAAGUUC -2.1 -2.40 -0.90 2.00 1.00 3.00 -39 58.00 5.40 4.00 II 52.60 47.20 71.75 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2966 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAACUUCAGGGUCAGCUU AAGCUGACCCUGAAGUUCA -0.9 -2.10 -0.90 1.00 1.00 3.00 -39 72.90 -4.00 6.00 II 47.40 60.00 91.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2967 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGAACUUCAGGGUCAGCU AGCUGACCCUGAAGUUCAU -2.1 -1.10 -0.60 3.00 3.00 3.00 -39.2 73.00 1.10 7.00 II 47.40 65.00 87.31 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2968 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGAACUUCAGGGUCAGC GCUGACCCUGAAGUUCAUC -3.4 -2.40 0.00 -1.00 2.00 3.00 -39.5 46.30 12.40 3.00 II 52.60 40.20 75.18 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2969 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGAUGAACUUCAGGGUCAG CUGACCCUGAAGUUCAUCU -2.1 -2.10 1.10 0.00 3.00 3.00 -38.2 46.60 -2.40 5.00 Ia 47.40 45.50 69.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2970 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGAUGAACUUCAGGGUCA UGACCCUGAAGUUCAUCUG -2.1 -2.10 1.10 -1.00 -3.00 3.00 -38.2 51.20 -10.70 5.00 II 47.40 45.20 50.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2971 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCAGAUGAACUUCAGGGUC GACCCUGAAGUUCAUCUGC -2.4 -3.40 1.20 0.00 1.00 3.00 -39.5 46.00 15.50 3.00 II 52.60 44.00 43.50 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2972 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCAGAUGAACUUCAGGGU ACCCUGAAGUUCAUCUGCA -2.2 -2.10 0.20 1.00 1.00 3.00 -39.2 67.00 -3.30 6.00 II 47.40 55.10 78.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2973 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGCAGAUGAACUUCAGGG CCCUGAAGUUCAUCUGCAC -3.3 -2.20 0.20 2.00 3.00 3.00 -39.2 61.10 5.00 4.00 II 52.60 56.00 79.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2974 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGCAGAUGAACUUCAGG CCUGAAGUUCAUCUGCACC -3.3 -3.30 0.20 0.00 2.00 2.00 -39.2 52.20 7.00 2.00 II 52.60 41.90 68.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2975 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGUGCAGAUGAACUUCAG CUGAAGUUCAUCUGCACCA -2.1 -2.10 0.20 0.00 2.00 2.00 -38 62.40 -2.60 5.00 II 47.40 55.20 67.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2976 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGUGCAGAUGAACUUCA UGAAGUUCAUCUGCACCAC -2.1 -2.20 0.20 1.00 -2.00 2.00 -38.1 49.00 -6.30 4.00 III 47.40 44.50 45.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2977 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGGUGCAGAUGAACUUC GAAGUUCAUCUGCACCACC -2.4 -3.30 0.20 0.00 0.00 2.00 -39.3 50.80 12.70 3.00 II 52.60 43.70 53.05 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2978 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGUGGUGCAGAUGAACUU AAGUUCAUCUGCACCACCG -0.9 -2.40 0.20 0.00 -3.00 3.00 -39.3 47.30 -6.00 3.00 III 52.60 37.40 58.69 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2979 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGGUGGUGCAGAUGAACU AGUUCAUCUGCACCACCGG -2.1 -3.30 0.20 0.00 -2.00 4.00 -41.7 44.60 -3.90 1.00 III 57.90 41.60 38.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2980 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGGUGGUGCAGAUGAAC GUUCAUCUGCACCACCGGC -2.2 -3.40 0.40 0.00 -1.00 5.00 -43 28.00 5.10 0.00 II 63.20 33.00 13.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2981 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCGGUGGUGCAGAUGAA UUCAUCUGCACCACCGGCA -0.9 -2.10 -0.60 2.00 -1.00 5.00 -42.9 35.40 -8.70 3.00 II 57.90 34.80 21.77 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2982 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGCCGGUGGUGCAGAUGA UCAUCUGCACCACCGGCAA -2.4 -0.90 -1.40 2.00 0.00 5.00 -42.9 50.70 -1.40 4.00 II 57.90 57.70 48.50 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2983 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGCCGGUGGUGCAGAUG CAUCUGCACCACCGGCAAG -2.1 -2.10 -1.40 -1.00 0.00 5.00 -42.6 46.20 1.00 1.00 II 63.20 44.80 40.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2984 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUUGCCGGUGGUGCAGAU AUCUGCACCACCGGCAAGC -1.1 -3.40 -1.40 0.00 -1.00 5.00 -43.9 35.50 -4.00 0.00 III 63.20 16.60 6.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2985 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUUGCCGGUGGUGCAGA UCUGCACCACCGGCAAGCU -2.4 -2.10 -1.40 2.00 0.00 5.00 -44.9 40.30 -1.40 2.00 II 63.20 37.50 4.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2986 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCUUGCCGGUGGUGCAG CUGCACCACCGGCAAGCUG -2.1 -2.10 -1.40 0.00 0.00 5.00 -44.6 39.80 1.00 1.00 II 68.40 39.60 32.40 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2987 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCAGCUUGCCGGUGGUGCA UGCACCACCGGCAAGCUGC -2.1 -3.40 -1.30 1.00 -1.00 5.00 -45.9 37.70 -3.80 0.00 III 68.40 29.10 3.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2988 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCAGCUUGCCGGUGGUGC GCACCACCGGCAAGCUGCC -3.4 -3.30 -3.20 2.00 1.00 5.00 -47.1 41.70 7.40 1.00 II 73.70 38.10 35.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2989 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCAGCUUGCCGGUGGUG CACCACCGGCAAGCUGCCC -2.1 -3.30 -4.00 0.00 0.00 5.00 -47 17.60 -2.00 -1.00 II 73.70 26.10 20.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2990 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGGCAGCUUGCCGGUGGU ACCACCGGCAAGCUGCCCG -2.2 -2.40 -4.00 -2.00 -2.00 5.00 -47.3 24.20 -5.90 -1.00 III 73.70 23.20 4.65 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2991 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGGGCAGCUUGCCGGUGG CCACCGGCAAGCUGCCCGU -3.3 -2.20 -4.00 2.00 2.00 5.00 -47.3 34.20 2.40 2.00 II 73.70 48.60 38.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2992 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACGGGCAGCUUGCCGGUG CACCGGCAAGCUGCCCGUG -2.1 -2.10 -4.00 0.00 0.00 5.00 -46.1 24.40 1.00 -1.00 II 73.70 37.40 19.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2993 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCACGGGCAGCUUGCCGGU ACCGGCAAGCUGCCCGUGC -2.2 -3.40 -4.00 0.00 0.00 5.00 -47.4 20.70 -3.30 0.00 III 73.70 27.50 16.84 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2994 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCACGGGCAGCUUGCCGG CCGGCAAGCUGCCCGUGCC -3.3 -3.30 -4.00 1.00 2.00 5.00 -48.5 40.20 0.00 1.00 II 78.90 40.50 46.16 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2995 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCACGGGCAGCUUGCCG CGGCAAGCUGCCCGUGCCC -2.4 -3.30 -4.00 2.00 2.00 5.00 -48.5 28.90 9.70 0.00 II 78.90 35.80 27.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2996 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGGCACGGGCAGCUUGCC GGCAAGCUGCCCGUGCCCU -3.3 -2.10 -3.70 2.00 3.00 5.00 -48.2 27.60 5.10 0.00 II 73.70 44.60 30.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2997 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGGCACGGGCAGCUUGC GCAAGCUGCCCGUGCCCUG -3.4 -2.10 -0.50 -1.00 0.00 5.00 -47 32.30 0.50 2.00 II 73.70 46.30 56.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2998 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAGGGCACGGGCAGCUUG CAAGCUGCCCGUGCCCUGG -2.1 -3.30 -0.50 0.00 -1.00 5.00 -46.9 25.00 0.40 1.00 II 73.70 37.60 46.31 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si2999 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCAGGGCACGGGCAGCUU AAGCUGCCCGUGCCCUGGC -0.9 -3.40 -1.90 0.00 -2.00 5.00 -48.2 19.40 -4.00 0.00 III 73.70 22.50 18.03 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3000 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCCAGGGCACGGGCAGCU AGCUGCCCGUGCCCUGGCC -2.1 -3.30 -2.70 1.00 -1.00 5.00 -50.6 12.70 -3.60 1.00 III 78.90 27.50 8.49 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3001 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCCAGGGCACGGGCAGC GCUGCCCGUGCCCUGGCCC -3.4 -3.30 -2.70 1.00 0.00 5.00 -51.8 11.80 7.40 -1.00 II 84.20 27.30 28.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3002 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGGCCAGGGCACGGGCAG CUGCCCGUGCCCUGGCCCA -2.1 -2.10 -2.70 0.00 2.00 5.00 -50.5 27.20 0.10 2.00 II 78.90 46.70 26.39 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3003 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGGCCAGGGCACGGGCA UGCCCGUGCCCUGGCCCAC -2.1 -2.20 -2.70 1.00 -1.00 5.00 -50.6 19.00 -8.70 -1.00 III 78.90 29.10 23.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3004 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGGGCCAGGGCACGGGC GCCCGUGCCCUGGCCCACC -3.4 -3.30 -2.70 0.00 2.00 5.00 -51.8 19.40 9.80 -1.00 II 84.20 33.00 14.96 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3005 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUGGGCCAGGGCACGGG CCCGUGCCCUGGCCCACCC -3.3 -3.30 -1.50 1.00 1.00 5.00 -51.7 19.90 0.00 1.00 II 84.20 34.60 8.36 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3006 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGGUGGGCCAGGGCACGG CCGUGCCCUGGCCCACCCU -3.3 -2.10 -1.50 1.00 3.00 5.00 -50.5 22.20 2.30 2.00 II 78.90 46.90 5.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3007 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAGGGUGGGCCAGGGCACG CGUGCCCUGGCCCACCCUC -2.4 -2.40 -1.50 0.00 1.00 5.00 -49.6 15.00 -2.40 0.00 II 78.90 38.80 29.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3008 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAGGGUGGGCCAGGGCAC GUGCCCUGGCCCACCCUCG -2.2 -2.40 -1.50 0.00 0.00 5.00 -49.6 15.30 -1.90 0.00 II 78.90 36.40 0.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3009 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGAGGGUGGGCCAGGGCA UGCCCUGGCCCACCCUCGU -2.1 -2.20 -1.50 2.00 0.00 5.00 -49.6 26.90 -3.70 2.00 II 73.70 40.50 0.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3010 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACGAGGGUGGGCCAGGGC GCCCUGGCCCACCCUCGUG -3.4 -2.10 -1.50 -1.00 1.00 5.00 -49.6 24.40 10.50 1.00 II 78.90 41.60 22.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3011 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCACGAGGGUGGGCCAGGG CCCUGGCCCACCCUCGUGA -3.3 -2.40 -1.00 2.00 4.00 5.00 -48.6 26.60 0.00 3.00 II 73.70 51.80 25.31 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3012 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCACGAGGGUGGGCCAGG CCUGGCCCACCCUCGUGAC -3.3 -2.20 -1.00 0.00 1.00 5.00 -47.5 26.00 0.00 1.00 II 73.70 41.40 30.95 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3013 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCACGAGGGUGGGCCAG CUGGCCCACCCUCGUGACC -2.1 -3.30 -1.00 1.00 1.00 5.00 -47.5 23.70 5.70 1.00 II 73.70 26.70 24.32 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3014 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGUCACGAGGGUGGGCCA UGGCCCACCCUCGUGACCA -2.1 -2.10 -1.00 -1.00 0.00 5.00 -47.5 41.00 -3.80 2.00 II 68.40 39.50 71.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3015 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGUCACGAGGGUGGGCC GGCCCACCCUCGUGACCAC -3.3 -2.20 -1.00 1.00 3.00 5.00 -47.6 43.10 9.70 2.00 II 73.70 50.90 50.96 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3016 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGGUCACGAGGGUGGGC GCCCACCCUCGUGACCACC -3.4 -3.30 -1.00 0.00 2.00 4.00 -47.6 26.40 9.70 -1.00 II 73.70 32.00 43.92 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3017 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUGGUCACGAGGGUGGG CCCACCCUCGUGACCACCC -3.3 -3.30 -1.00 0.00 1.00 3.00 -47.5 26.70 0.00 0.00 II 73.70 31.00 20.39 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3018 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGGUGGUCACGAGGGUGG CCACCCUCGUGACCACCCU -3.3 -2.10 -1.00 1.00 2.00 3.00 -46.3 39.00 -4.90 4.00 II 68.40 52.70 33.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3019 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGGUGGUCACGAGGGUG CACCCUCGUGACCACCCUG -2.1 -2.10 -0.70 -1.00 0.00 3.00 -45.1 31.40 -2.10 1.00 II 68.40 44.20 26.50 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3020 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCAGGGUGGUCACGAGGGU ACCCUCGUGACCACCCUGA -2.2 -2.40 1.10 1.00 2.00 3.00 -45.4 29.50 -3.90 4.00 II 63.20 46.40 37.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3021 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCAGGGUGGUCACGAGGG CCCUCGUGACCACCCUGAC -3.3 -2.20 1.10 1.00 2.00 3.00 -45.4 35.40 -4.90 2.00 II 68.40 47.50 42.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3022 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCAGGGUGGUCACGAGG CCUCGUGACCACCCUGACC -3.3 -3.30 1.10 1.00 1.00 3.00 -45.4 35.20 8.10 2.00 II 68.40 39.40 50.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3023 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGUCAGGGUGGUCACGAG CUCGUGACCACCCUGACCU -2.1 -2.10 1.10 2.00 2.00 3.00 -44.2 44.10 0.00 3.00 II 63.20 39.30 56.98 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3024 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGGUCAGGGUGGUCACGA UCGUGACCACCCUGACCUA -2.4 -1.30 1.10 1.00 2.00 3.00 -43.4 49.80 -1.40 5.00 II 57.90 59.90 51.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3025 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGGUCAGGGUGGUCACG CGUGACCACCCUGACCUAC -2.4 -2.20 1.10 0.00 2.00 3.00 -43.2 37.30 3.00 1.00 II 63.20 43.70 47.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3026 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUAGGUCAGGGUGGUCAC GUGACCACCCUGACCUACG -2.2 -2.40 1.30 -1.00 0.00 3.00 -43.2 47.30 5.40 2.00 II 63.20 38.70 66.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3027 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUAGGUCAGGGUGGUCA UGACCACCCUGACCUACGG -2.1 -3.30 0.60 0.00 -3.00 3.00 -44.3 44.30 -0.70 4.00 III 63.20 36.40 41.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3028 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUAGGUCAGGGUGGUC GACCACCCUGACCUACGGC -2.4 -3.40 0.20 -1.00 0.00 4.00 -45.6 24.70 9.70 1.00 II 68.40 27.40 30.04 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3029 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCCGUAGGUCAGGGUGGU ACCACCCUGACCUACGGCG -2.2 -2.40 0.20 0.00 -2.00 5.00 -45.6 20.10 -8.30 0.00 III 68.40 24.30 45.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3030 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGCCGUAGGUCAGGGUGG CCACCCUGACCUACGGCGU -3.3 -2.20 0.20 3.00 2.00 5.00 -45.6 33.50 -4.90 3.00 II 68.40 50.00 56.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3031 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACGCCGUAGGUCAGGGUG CACCCUGACCUACGGCGUG -2.1 -2.10 0.20 -1.00 0.00 5.00 -44.4 46.10 3.40 1.00 II 68.40 41.60 74.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3032 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCACGCCGUAGGUCAGGGU ACCCUGACCUACGGCGUGC -2.2 -3.40 0.20 1.00 0.00 5.00 -45.7 31.00 -4.00 1.00 III 68.40 27.40 67.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3033 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCACGCCGUAGGUCAGGG CCCUGACCUACGGCGUGCA -3.3 -2.10 0.20 1.00 4.00 5.00 -45.6 47.90 4.60 3.00 II 68.40 53.20 55.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3034 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGCACGCCGUAGGUCAGG CCUGACCUACGGCGUGCAG -3.3 -2.10 0.30 0.00 0.00 5.00 -44.4 27.60 0.70 2.00 II 68.40 44.20 47.98 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3035 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUGCACGCCGUAGGUCAG CUGACCUACGGCGUGCAGU -2.1 -2.20 0.60 1.00 3.00 5.00 -43.3 41.50 0.40 2.00 II 63.20 38.10 56.34 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3036 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACUGCACGCCGUAGGUCA UGACCUACGGCGUGCAGUG -2.1 -2.10 0.30 0.00 -3.00 5.00 -43.3 47.10 -8.10 3.00 III 63.20 38.30 57.96 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3037 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCACUGCACGCCGUAGGUC GACCUACGGCGUGCAGUGC -2.4 -3.40 0.10 2.00 2.00 5.00 -44.6 29.30 5.00 1.00 II 68.40 36.00 60.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3038 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCACUGCACGCCGUAGGU ACCUACGGCGUGCAGUGCU -2.2 -2.10 -1.50 0.00 1.00 5.00 -44.3 46.80 -3.90 2.00 II 63.20 39.40 55.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3039 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AAGCACUGCACGCCGUAGG CCUACGGCGUGCAGUGCUU -3.3 -0.90 -1.60 4.00 3.00 5.00 -43 54.80 2.80 4.00 Ib 63.20 59.80 70.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3040 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAAGCACUGCACGCCGUAG CUACGGCGUGCAGUGCUUC -2.1 -2.40 -1.60 1.00 1.00 5.00 -42.1 42.00 -0.10 1.00 II 63.20 37.00 59.69 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3041 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAAGCACUGCACGCCGUA UACGGCGUGCAGUGCUUCA -1.3 -2.10 -1.60 -1.00 0.00 5.00 -42.1 41.60 -3.70 4.00 II 57.90 48.90 56.49 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3042 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGAAGCACUGCACGCCGU ACGGCGUGCAGUGCUUCAG -2.2 -2.10 -1.60 0.00 -1.00 5.00 -42.9 38.70 -8.20 1.00 III 63.20 40.50 62.10 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3043 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUGAAGCACUGCACGCCG CGGCGUGCAGUGCUUCAGC -2.4 -3.40 -1.60 0.00 2.00 5.00 -44.1 29.80 5.10 1.00 II 68.40 41.40 59.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3044 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCUGAAGCACUGCACGCC GGCGUGCAGUGCUUCAGCC -3.3 -3.30 -2.10 1.00 1.00 4.00 -45 38.30 8.10 1.00 II 68.40 41.20 71.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3045 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGCUGAAGCACUGCACGC GCGUGCAGUGCUUCAGCCG -3.4 -2.40 -0.80 0.00 0.00 4.00 -44.1 36.00 5.40 1.00 II 68.40 43.90 50.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3046 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGCUGAAGCACUGCACG CGUGCAGUGCUUCAGCCGC -2.4 -3.40 -0.30 0.00 1.00 5.00 -44.1 37.70 2.40 0.00 II 68.40 41.90 79.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3047 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCGGCUGAAGCACUGCAC GUGCAGUGCUUCAGCCGCU -2.2 -2.10 -0.60 2.00 2.00 5.00 -43.8 48.60 2.50 3.00 II 63.20 49.80 90.24 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3048 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGCGGCUGAAGCACUGCA UGCAGUGCUUCAGCCGCUA -2.1 -1.30 -1.30 2.00 1.00 5.00 -42.9 50.40 1.00 3.00 II 57.90 55.90 81.99 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3049 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGCGGCUGAAGCACUGC GCAGUGCUUCAGCCGCUAC -3.4 -2.20 -1.30 0.00 2.00 5.00 -43 39.80 9.70 2.00 II 63.20 50.40 73.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3050 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUAGCGGCUGAAGCACUG CAGUGCUUCAGCCGCUACC -2.1 -3.30 -1.30 0.00 1.00 5.00 -42.9 34.90 -2.60 1.00 II 63.20 36.50 81.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3051 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUAGCGGCUGAAGCACU AGUGCUUCAGCCGCUACCC -2.1 -3.30 -1.00 1.00 -2.00 5.00 -44.1 29.20 -3.90 0.00 III 63.20 32.40 87.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3052 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGGUAGCGGCUGAAGCAC GUGCUUCAGCCGCUACCCC -2.2 -3.30 -0.30 1.00 0.00 5.00 -45.3 26.80 8.10 1.00 II 68.40 32.90 58.04 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3053 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGGGUAGCGGCUGAAGCA UGCUUCAGCCGCUACCCCG -2.1 -2.40 -0.30 -1.00 -3.00 5.00 -45.5 28.50 -8.10 0.00 III 68.40 32.20 58.61 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3054 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGGGGUAGCGGCUGAAGC GCUUCAGCCGCUACCCCGA -3.4 -2.40 -0.30 2.00 3.00 5.00 -45.8 46.30 12.10 3.00 II 68.40 60.40 76.26 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3055 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGGGGUAGCGGCUGAAG CUUCAGCCGCUACCCCGAC -2.1 -2.20 0.90 0.00 0.00 5.00 -44.6 30.60 -2.40 1.00 II 68.40 35.10 60.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3056 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCGGGGUAGCGGCUGAA UUCAGCCGCUACCCCGACC -0.9 -3.30 0.90 0.00 -2.00 5.00 -45.8 19.80 -6.10 2.00 III 68.40 17.90 36.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3057 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGUCGGGGUAGCGGCUGA UCAGCCGCUACCCCGACCA -2.4 -2.10 0.90 0.00 -1.00 5.00 -47 38.80 1.00 5.00 II 68.40 39.90 58.40 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3058 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGUCGGGGUAGCGGCUG CAGCCGCUACCCCGACCAC -2.1 -2.20 0.90 1.00 1.00 5.00 -46.8 25.50 0.00 2.00 II 73.70 42.20 37.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3059 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUGGUCGGGGUAGCGGCU AGCCGCUACCCCGACCACA -2.1 -2.10 0.90 0.00 2.00 5.00 -46.8 38.40 -3.50 3.00 II 68.40 48.70 33.58 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3060 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGUGGUCGGGGUAGCGGC GCCGCUACCCCGACCACAU -3.4 -1.10 0.90 3.00 4.00 5.00 -45.8 49.50 7.40 4.00 Ib 68.40 61.00 44.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3061 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAUGUGGUCGGGGUAGCGG CCGCUACCCCGACCACAUG -3.3 -2.10 0.90 0.00 3.00 5.00 -44.5 42.60 0.30 3.00 II 68.40 49.50 44.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3062 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCAUGUGGUCGGGGUAGCG CGCUACCCCGACCACAUGA -2.4 -2.40 1.20 -1.00 4.00 5.00 -43.6 44.50 0.00 5.00 Ib 63.20 58.20 40.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3063 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCAUGUGGUCGGGGUAGC GCUACCCCGACCACAUGAA -3.4 -0.90 2.80 1.00 3.00 5.00 -42.1 56.00 5.10 6.00 Ia 57.90 63.00 44.75 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3064 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUCAUGUGGUCGGGGUAG CUACCCCGACCACAUGAAG -2.1 -2.10 2.80 0.00 0.00 5.00 -40.8 43.60 -1.70 4.00 II 57.90 44.00 39.67 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3065 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUUCAUGUGGUCGGGGUA UACCCCGACCACAUGAAGC -1.3 -3.40 2.80 0.00 -2.00 5.00 -42.1 46.20 1.70 2.00 II 57.90 22.30 30.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3066 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCUUCAUGUGGUCGGGGU ACCCCGACCACAUGAAGCA -2.2 -2.10 2.80 1.00 1.00 5.00 -42.9 65.00 -4.00 5.00 II 57.90 50.40 62.79 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3067 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGCUUCAUGUGGUCGGGG CCCCGACCACAUGAAGCAG -3.3 -2.10 2.80 0.00 2.00 5.00 -42.8 43.80 0.30 1.00 II 63.20 48.80 32.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3068 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUGCUUCAUGUGGUCGGG CCCGACCACAUGAAGCAGC -3.3 -3.40 2.80 0.00 2.00 4.00 -42.9 46.10 3.00 1.00 II 63.20 35.00 40.48 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3069 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCUGCUUCAUGUGGUCGG CCGACCACAUGAAGCAGCA -3.3 -2.10 2.20 1.00 3.00 3.00 -41.7 66.30 0.00 5.00 II 57.90 62.10 50.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3070 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGCUGCUUCAUGUGGUCG CGACCACAUGAAGCAGCAC -2.4 -2.20 1.70 1.00 2.00 2.00 -40.6 58.60 7.70 2.00 II 57.90 48.30 62.39 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3071 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUGCUGCUUCAUGUGGUC GACCACAUGAAGCAGCACG -2.4 -2.40 1.70 -2.00 0.00 2.00 -40.6 47.50 3.10 1.00 II 57.90 39.10 50.06 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3072 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGUGCUGCUUCAUGUGGU ACCACAUGAAGCAGCACGA -2.2 -2.40 1.70 2.00 2.00 2.00 -40.6 61.30 -6.60 5.00 II 52.60 55.50 70.72 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3073 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGUGCUGCUUCAUGUGG CCACAUGAAGCAGCACGAC -3.3 -2.20 1.70 1.00 1.00 2.00 -40.6 52.60 5.40 2.00 II 57.90 44.60 67.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3074 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUCGUGCUGCUUCAUGUG CACAUGAAGCAGCACGACU -2.1 -2.10 1.70 2.00 3.00 2.00 -39.4 59.40 0.70 4.00 II 52.60 52.80 64.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3075 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AAGUCGUGCUGCUUCAUGU ACAUGAAGCAGCACGACUU -2.2 -0.90 1.60 3.00 2.00 2.00 -38.2 77.40 -4.00 6.00 II 47.40 58.10 82.71 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3076 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAAGUCGUGCUGCUUCAUG CAUGAAGCAGCACGACUUC -2.1 -2.40 -0.90 1.00 2.00 2.00 -38.4 56.80 4.70 4.00 II 52.60 48.90 66.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3077 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGAAGUCGUGCUGCUUCAU AUGAAGCAGCACGACUUCU -1.1 -2.10 -2.10 1.00 1.00 2.00 -38.4 55.10 -3.30 3.00 II 47.40 42.50 67.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3078 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AAGAAGUCGUGCUGCUUCA UGAAGCAGCACGACUUCUU -2.1 -0.90 -2.10 2.00 0.00 2.00 -38.2 62.40 -3.40 6.00 II 47.40 51.80 63.55 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3079 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAAGAAGUCGUGCUGCUUC GAAGCAGCACGACUUCUUC -2.4 -2.40 -2.10 1.00 2.00 2.00 -38.5 54.60 14.80 4.00 II 52.60 51.90 64.69 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3080 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAAGAAGUCGUGCUGCUU AAGCAGCACGACUUCUUCA -0.9 -2.10 1.00 0.00 1.00 2.00 -38.2 57.90 -1.00 6.00 II 47.40 54.20 50.99 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3081 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGAAGAAGUCGUGCUGCU AGCAGCACGACUUCUUCAA -2.1 -0.90 1.00 0.00 2.00 2.00 -38.2 59.20 -3.60 7.00 II 47.40 61.60 52.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3082 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGAAGAAGUCGUGCUGC GCAGCACGACUUCUUCAAG -3.4 -2.10 1.00 -1.00 2.00 2.00 -38.2 51.20 8.10 5.00 II 52.60 54.20 63.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3083 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUUGAAGAAGUCGUGCUG CAGCACGACUUCUUCAAGU -2.1 -2.20 0.40 0.00 3.00 2.00 -37 61.20 5.40 6.00 Ia 47.40 50.20 77.79 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3084 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GACUUGAAGAAGUCGUGCU AGCACGACUUCUUCAAGUC -2.1 -2.40 -2.40 1.00 0.00 2.00 -37.3 67.30 -1.70 4.00 II 47.40 46.60 76.48 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3085 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGACUUGAAGAAGUCGUGC GCACGACUUCUUCAAGUCC -3.4 -3.30 -3.20 1.00 2.00 2.00 -38.5 53.70 12.00 3.00 II 52.60 48.60 78.22 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3086 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGACUUGAAGAAGUCGUG CACGACUUCUUCAAGUCCG -2.1 -2.40 -3.20 -1.00 -1.00 3.00 -37.5 53.50 -4.60 2.00 II 52.60 44.70 75.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3087 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGACUUGAAGAAGUCGU ACGACUUCUUCAAGUCCGC -2.2 -3.40 -3.20 2.00 -1.00 4.00 -38.8 49.10 -1.60 2.00 III 52.60 39.90 52.06 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3088 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCGGACUUGAAGAAGUCG CGACUUCUUCAAGUCCGCC -2.4 -3.30 -3.20 0.00 0.00 5.00 -39.9 35.80 2.30 -1.00 II 57.90 37.00 44.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3089 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGCGGACUUGAAGAAGUC GACUUCUUCAAGUCCGCCA -2.4 -2.10 -2.90 0.00 2.00 5.00 -39.6 43.70 4.80 3.00 II 52.60 56.90 56.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3090 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGGCGGACUUGAAGAAGU ACUUCUUCAAGUCCGCCAU -2.2 -1.10 0.70 2.00 1.00 5.00 -38.3 50.90 -6.60 4.00 II 47.40 56.40 58.93 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3091 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAUGGCGGACUUGAAGAAG CUUCUUCAAGUCCGCCAUG -2.1 -2.10 1.90 -1.00 0.00 5.00 -38.2 44.40 1.00 3.00 II 52.60 42.70 51.38 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3092 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCAUGGCGGACUUGAAGAA UUCUUCAAGUCCGCCAUGC -0.9 -3.40 2.00 0.00 -2.00 5.00 -39.5 38.00 -3.10 3.00 III 52.60 20.70 31.18 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3093 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCAUGGCGGACUUGAAGA UCUUCAAGUCCGCCAUGCC -2.4 -3.30 1.20 1.00 -2.00 5.00 -41.9 50.20 -1.50 2.00 III 57.90 33.10 43.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3094 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCAUGGCGGACUUGAAG CUUCAAGUCCGCCAUGCCC -2.1 -3.30 1.20 2.00 0.00 5.00 -42.8 40.90 7.40 1.00 II 63.20 34.50 51.05 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3095 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGGCAUGGCGGACUUGAA UUCAAGUCCGCCAUGCCCG -0.9 -2.40 1.20 1.00 -4.00 5.00 -43.1 33.80 -8.30 0.00 III 63.20 21.60 37.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3096 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGGGCAUGGCGGACUUGA UCAAGUCCGCCAUGCCCGA -2.4 -2.40 1.20 1.00 -1.00 5.00 -44.6 38.30 -6.10 4.00 II 63.20 48.30 47.23 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3097 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCGGGCAUGGCGGACUUG CAAGUCCGCCAUGCCCGAA -2.1 -0.90 1.20 -1.00 2.00 5.00 -43.1 37.80 -2.40 4.00 II 63.20 54.70 48.80 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3098 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUCGGGCAUGGCGGACUU AAGUCCGCCAUGCCCGAAG -0.9 -2.10 1.20 -1.00 -1.00 5.00 -43.1 34.60 -3.60 2.00 III 63.20 33.70 40.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3099 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUUCGGGCAUGGCGGACU AGUCCGCCAUGCCCGAAGG -2.1 -3.30 1.10 0.00 -2.00 5.00 -45.5 37.80 -6.00 3.00 III 68.40 38.90 47.08 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3100 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCUUCGGGCAUGGCGGAC GUCCGCCAUGCCCGAAGGC -2.2 -3.40 -2.10 0.00 0.00 5.00 -46.8 30.90 12.70 1.00 II 73.70 25.40 86.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3101 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCCUUCGGGCAUGGCGGA UCCGCCAUGCCCGAAGGCU -2.4 -2.10 -3.30 2.00 0.00 5.00 -46.7 29.80 -6.10 1.00 II 68.40 31.40 46.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3102 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGCCUUCGGGCAUGGCGG CCGCCAUGCCCGAAGGCUA -3.3 -1.30 -3.30 3.00 5.00 5.00 -45.6 58.20 -2.60 3.00 Ib 68.40 69.10 67.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3103 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGCCUUCGGGCAUGGCG CGCCAUGCCCGAAGGCUAC -2.4 -2.20 -3.30 2.00 3.00 5.00 -44.5 50.30 2.40 1.00 II 68.40 51.50 61.92 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3104 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUAGCCUUCGGGCAUGGC GCCAUGCCCGAAGGCUACG -3.4 -2.40 -3.30 -1.00 1.00 5.00 -44.5 40.00 5.40 0.00 II 68.40 36.60 67.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3105 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGUAGCCUUCGGGCAUGG CCAUGCCCGAAGGCUACGU -3.3 -2.20 -3.30 0.00 2.00 5.00 -43.3 36.70 0.40 3.00 II 63.20 44.00 55.84 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3106 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GACGUAGCCUUCGGGCAUG CAUGCCCGAAGGCUACGUC -2.1 -2.40 -3.30 0.00 0.00 5.00 -42.4 33.00 -2.40 1.00 II 63.20 37.10 37.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3107 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGACGUAGCCUUCGGGCAU AUGCCCGAAGGCUACGUCC -1.1 -3.30 -3.30 1.00 -1.00 5.00 -43.6 33.30 1.50 0.00 III 63.20 28.10 17.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3108 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGACGUAGCCUUCGGGCA UGCCCGAAGGCUACGUCCA -2.1 -2.10 -3.30 2.00 0.00 5.00 -44.6 55.40 -3.10 3.00 II 63.20 52.20 53.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3109 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGGACGUAGCCUUCGGGC GCCCGAAGGCUACGUCCAG -3.4 -2.10 -3.30 -1.00 2.00 5.00 -44.6 46.50 5.70 1.00 II 68.40 51.00 39.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3110 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUGGACGUAGCCUUCGGG CCCGAAGGCUACGUCCAGG -3.3 -3.30 -0.30 -1.00 2.00 4.00 -44.5 37.80 0.40 1.00 II 68.40 38.00 44.19 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3111 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCUGGACGUAGCCUUCGG CCGAAGGCUACGUCCAGGA -3.3 -2.40 -0.30 1.00 3.00 3.00 -43.6 52.70 4.70 4.00 II 63.20 55.70 37.91 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3112 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCCUGGACGUAGCCUUCG CGAAGGCUACGUCCAGGAG -2.4 -2.10 -0.30 1.00 0.00 3.00 -42.4 42.00 -2.00 3.00 II 63.20 53.10 43.91 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3113 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUCCUGGACGUAGCCUUC GAAGGCUACGUCCAGGAGC -2.4 -3.40 -0.30 0.00 0.00 3.00 -43.4 44.10 7.80 2.00 II 63.20 36.70 38.30 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3114 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCUCCUGGACGUAGCCUU AAGGCUACGUCCAGGAGCG -0.9 -2.40 -1.40 1.00 -3.00 3.00 -43.4 49.70 -8.30 1.00 III 63.20 35.70 50.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3115 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGCUCCUGGACGUAGCCU AGGCUACGUCCAGGAGCGC -2.1 -3.40 -1.40 2.00 0.00 4.00 -45.9 33.90 -1.70 -1.00 III 68.40 30.10 43.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3116 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCGCUCCUGGACGUAGCC GGCUACGUCCAGGAGCGCA -3.3 -2.10 -1.40 -1.00 3.00 4.00 -45.9 46.90 9.80 1.00 II 68.40 55.50 68.67 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3117 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGCGCUCCUGGACGUAGC GCUACGUCCAGGAGCGCAC -3.4 -2.20 -1.40 3.00 1.00 4.00 -44.8 45.30 4.80 0.00 II 68.40 45.60 57.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3118 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGCGCUCCUGGACGUAG CUACGUCCAGGAGCGCACC -2.1 -3.30 -0.60 1.00 0.00 4.00 -44.7 34.40 0.00 1.00 II 68.40 32.70 45.22 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3119 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGUGCGCUCCUGGACGUA UACGUCCAGGAGCGCACCA -1.3 -2.10 -0.90 -1.00 -1.00 4.00 -44.7 36.30 -3.10 4.00 II 63.20 38.50 37.43 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3120 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGGUGCGCUCCUGGACGU ACGUCCAGGAGCGCACCAU -2.2 -1.10 -0.90 1.00 2.00 4.00 -44.5 41.20 -8.70 3.00 II 63.20 46.30 67.79 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3121 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGGUGCGCUCCUGGACG CGUCCAGGAGCGCACCAUC -2.4 -2.40 -0.90 1.00 3.00 4.00 -44.7 44.10 2.40 2.00 II 68.40 49.80 54.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3122 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGAUGGUGCGCUCCUGGAC GUCCAGGAGCGCACCAUCU -2.2 -2.10 -0.90 3.00 3.00 4.00 -44.4 52.00 10.50 4.00 Ib 63.20 51.10 79.03 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3123 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AAGAUGGUGCGCUCCUGGA UCCAGGAGCGCACCAUCUU -2.4 -0.90 -0.90 2.00 1.00 4.00 -43.1 55.10 -6.10 5.00 II 57.90 49.10 68.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3124 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAAGAUGGUGCGCUCCUGG CCAGGAGCGCACCAUCUUC -3.3 -2.40 -0.90 0.00 3.00 4.00 -43.1 46.10 5.10 4.00 II 63.20 51.20 56.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3125 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGAAGAUGGUGCGCUCCUG CAGGAGCGCACCAUCUUCU -2.1 -2.10 -1.70 3.00 3.00 4.00 -41.9 45.30 -2.40 3.00 Ia 57.90 50.90 56.80 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3126 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AAGAAGAUGGUGCGCUCCU AGGAGCGCACCAUCUUCUU -2.1 -0.90 -1.50 1.00 2.00 4.00 -40.7 50.10 1.10 5.00 II 52.60 56.90 93.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3127 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAAGAAGAUGGUGCGCUCC GGAGCGCACCAUCUUCUUC -3.3 -2.40 -1.00 0.00 2.00 4.00 -41 46.90 13.10 3.00 II 57.90 51.60 60.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3128 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAAGAAGAUGGUGCGCUC GAGCGCACCAUCUUCUUCA -2.4 -2.10 0.90 -1.00 3.00 4.00 -39.8 54.70 7.40 6.00 Ia 52.60 58.70 72.63 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3129 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGAAGAAGAUGGUGCGCU AGCGCACCAUCUUCUUCAA -2.1 -0.90 3.40 1.00 3.00 4.00 -38.3 61.60 1.10 8.00 II 47.40 70.50 74.80 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3130 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGAAGAAGAUGGUGCGC GCGCACCAUCUUCUUCAAG -3.4 -2.10 2.40 -2.00 2.00 4.00 -38.3 47.30 13.40 4.00 II 52.60 47.60 49.89 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3131 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUUGAAGAAGAUGGUGCG CGCACCAUCUUCUUCAAGG -2.4 -3.30 1.10 -2.00 1.00 3.00 -38.2 52.50 -2.00 4.00 II 52.60 43.90 70.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3132 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCUUGAAGAAGAUGGUGC GCACCAUCUUCUUCAAGGA -3.4 -2.40 0.20 1.00 3.00 2.00 -38.2 74.70 9.40 8.00 Ib 47.40 69.50 79.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3133 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCCUUGAAGAAGAUGGUG CACCAUCUUCUUCAAGGAC -2.1 -2.20 0.00 1.00 1.00 2.00 -37 52.60 2.30 3.00 II 47.40 45.90 57.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3134 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCCUUGAAGAAGAUGGU ACCAUCUUCUUCAAGGACG -2.2 -2.40 0.00 0.00 -1.00 2.00 -37.3 53.60 -8.60 3.00 III 47.40 37.90 60.43 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3135 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGUCCUUGAAGAAGAUGG CCAUCUUCUUCAAGGACGA -3.3 -2.40 0.00 2.00 2.00 2.00 -37.5 77.70 -0.30 7.00 II 47.40 69.70 82.71 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3136 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGUCCUUGAAGAAGAUG CAUCUUCUUCAAGGACGAC -2.1 -2.20 0.00 0.00 0.00 2.00 -36.4 52.60 2.30 2.00 II 47.40 43.70 40.19 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3137 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCGUCCUUGAAGAAGAU AUCUUCUUCAAGGACGACG -1.1 -2.40 0.00 -1.00 -2.00 2.00 -36.7 40.80 -8.60 1.00 III 47.40 25.70 37.67 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3138 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUCGUCCUUGAAGAAGA UCUUCUUCAAGGACGACGG -2.4 -3.30 0.30 1.00 -4.00 3.00 -38.9 47.90 -8.30 2.00 III 52.60 37.30 29.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3139 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUCGUCCUUGAAGAAG CUUCUUCAAGGACGACGGC -2.1 -3.40 0.30 1.00 -1.00 4.00 -39.9 42.10 3.00 1.00 II 57.90 34.10 31.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3140 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCGUCGUCCUUGAAGAA UUCUUCAAGGACGACGGCA -0.9 -2.10 0.30 0.00 -1.00 4.00 -39.9 47.70 -3.10 3.00 II 52.60 35.40 44.72 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3141 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGCCGUCGUCCUUGAAGA UCUUCAAGGACGACGGCAA -2.4 -0.90 0.50 3.00 1.00 4.00 -39.9 65.60 -6.10 5.00 II 52.60 58.70 69.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3142 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGCCGUCGUCCUUGAAG CUUCAAGGACGACGGCAAC -2.1 -2.20 1.30 1.00 2.00 4.00 -39.7 58.40 2.40 2.00 II 57.90 45.20 57.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3143 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUUGCCGUCGUCCUUGAA UUCAAGGACGACGGCAACU -0.9 -2.10 1.30 1.00 0.00 4.00 -39.7 57.40 1.70 4.00 II 52.60 30.30 53.96 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3144 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGUUGCCGUCGUCCUUGA UCAAGGACGACGGCAACUA -2.4 -1.30 1.50 1.00 0.00 4.00 -40.1 65.10 -6.10 7.00 II 52.60 52.80 72.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3145 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGUUGCCGUCGUCCUUG CAAGGACGACGGCAACUAC -2.1 -2.20 1.60 1.00 2.00 4.00 -39.9 53.10 0.00 4.00 II 57.90 55.60 47.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3146 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUAGUUGCCGUCGUCCUU AAGGACGACGGCAACUACA -0.9 -2.10 1.60 1.00 1.00 4.00 -39.9 65.10 1.50 6.00 II 52.60 53.80 63.40 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3147 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUAGUUGCCGUCGUCCU AGGACGACGGCAACUACAA -2.1 -0.90 1.90 2.00 2.00 4.00 -39.9 69.80 -3.60 7.00 II 52.60 66.00 62.52 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3148 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGUAGUUGCCGUCGUCC GGACGACGGCAACUACAAG -3.3 -2.10 3.10 -1.00 2.00 4.00 -39.9 56.80 3.00 4.00 II 57.90 57.90 53.23 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3149 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCUUGUAGUUGCCGUCGUC GACGACGGCAACUACAAGA -2.4 -2.40 2.30 -1.00 3.00 4.00 -39 61.20 7.50 6.00 Ia 52.60 57.60 57.85 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3150 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCUUGUAGUUGCCGUCGU ACGACGGCAACUACAAGAC -2.2 -2.20 2.30 2.00 0.00 4.00 -38.8 56.90 -1.60 4.00 II 52.60 40.90 44.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3151 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCUUGUAGUUGCCGUCG CGACGGCAACUACAAGACC -2.4 -3.30 1.90 1.00 1.00 4.00 -39.9 55.90 3.00 3.00 II 57.90 48.30 80.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3152 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUCUUGUAGUUGCCGUC GACGGCAACUACAAGACCC -2.4 -3.30 1.10 0.00 0.00 4.00 -40.8 62.10 10.40 2.00 II 57.90 43.40 70.03 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3153 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGGUCUUGUAGUUGCCGU ACGGCAACUACAAGACCCG -2.2 -2.40 -0.20 1.00 -1.00 4.00 -40.8 57.20 -1.30 1.00 III 57.90 39.50 69.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3154 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGGUCUUGUAGUUGCCG CGGCAACUACAAGACCCGC -2.4 -3.40 -0.10 0.00 2.00 5.00 -42 36.80 2.30 -1.00 II 63.20 41.90 49.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3155 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCGGGUCUUGUAGUUGCC GGCAACUACAAGACCCGCG -3.3 -2.40 0.20 -1.00 0.00 6.00 -42 42.40 5.80 0.00 II 63.20 41.00 50.65 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3156 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGCGGGUCUUGUAGUUGC GCAACUACAAGACCCGCGC -3.4 -3.40 0.20 2.00 0.00 7.00 -42.1 40.50 7.40 1.00 II 63.20 40.60 47.84 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3157 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCGCGGGUCUUGUAGUUG CAACUACAAGACCCGCGCC -2.1 -3.30 2.30 0.00 0.00 8.00 -42 39.00 5.40 1.00 II 63.20 35.10 53.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3158 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGCGCGGGUCUUGUAGUU AACUACAAGACCCGCGCCG -0.9 -2.40 2.30 0.00 -3.00 9.00 -42.3 32.20 -5.30 0.00 III 63.20 24.20 34.59 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3159 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGGCGCGGGUCUUGUAGU ACUACAAGACCCGCGCCGA -2.2 -2.40 1.90 1.00 1.00 9.00 -43.8 46.70 -4.00 2.00 II 63.20 49.50 54.04 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3160 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGGCGCGGGUCUUGUAG CUACAAGACCCGCGCCGAG -2.1 -2.10 1.90 0.00 0.00 9.00 -43.7 47.50 5.80 2.00 II 68.40 39.90 74.80 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3161 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUCGGCGCGGGUCUUGUA UACAAGACCCGCGCCGAGG -1.3 -3.30 0.10 1.00 -3.00 9.00 -44.9 30.70 -5.80 0.00 III 68.40 21.90 52.18 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3162 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACCUCGGCGCGGGUCUUGU ACAAGACCCGCGCCGAGGU -2.2 -2.20 -0.80 2.00 1.00 9.00 -45.8 43.50 -1.60 4.00 II 68.40 39.40 58.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3163 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACCUCGGCGCGGGUCUUG CAAGACCCGCGCCGAGGUG -2.1 -2.10 -1.50 0.00 -1.00 9.00 -45.7 30.10 -4.40 2.00 II 73.70 37.30 44.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3164 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCACCUCGGCGCGGGUCUU AAGACCCGCGCCGAGGUGA -0.9 -2.40 -2.50 1.00 1.00 9.00 -46 33.80 -6.30 2.00 II 68.40 41.00 47.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3165 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCACCUCGGCGCGGGUCU AGACCCGCGCCGAGGUGAA -2.1 -0.90 -2.50 1.00 1.00 9.00 -46 54.50 -3.90 5.00 II 68.40 57.10 79.32 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3166 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUCACCUCGGCGCGGGUC GACCCGCGCCGAGGUGAAG -2.4 -2.10 -2.50 1.00 1.00 9.00 -46 38.40 5.80 1.00 II 73.70 42.40 71.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3167 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUUCACCUCGGCGCGGGU ACCCGCGCCGAGGUGAAGU -2.2 -2.20 -2.50 0.00 2.00 9.00 -45.8 38.20 -1.60 2.00 II 68.40 32.90 57.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3168 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AACUUCACCUCGGCGCGGG CCCGCGCCGAGGUGAAGUU -3.3 -0.90 -2.50 2.00 4.00 9.00 -44.5 49.80 -2.40 4.00 Ia 68.40 54.20 54.95 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3169 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAACUUCACCUCGGCGCGG CCGCGCCGAGGUGAAGUUC -3.3 -2.40 -2.50 1.00 3.00 8.00 -43.6 32.40 -2.40 1.00 II 68.40 43.30 28.13 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3170 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAACUUCACCUCGGCGCG CGCGCCGAGGUGAAGUUCG -2.4 -2.40 -2.50 -1.00 1.00 7.00 -42.7 48.30 1.10 1.00 II 68.40 45.70 76.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3171 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGAACUUCACCUCGGCGC GCGCCGAGGUGAAGUUCGA -3.4 -2.40 -2.50 2.00 3.00 6.00 -42.7 65.50 5.40 5.00 Ib 63.20 69.00 87.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3172 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGAACUUCACCUCGGCG CGCCGAGGUGAAGUUCGAG -2.4 -2.10 -2.30 -1.00 2.00 5.00 -41.4 48.40 5.40 0.00 II 63.20 47.10 66.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3173 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUCGAACUUCACCUCGGC GCCGAGGUGAAGUUCGAGG -3.4 -3.30 -1.70 0.00 1.00 4.00 -42.3 37.10 5.50 0.00 II 63.20 40.30 47.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3174 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCUCGAACUUCACCUCGG CCGAGGUGAAGUUCGAGGG -3.3 -3.30 -1.70 0.00 0.00 3.00 -42.2 43.80 -6.90 0.00 II 63.20 44.40 65.11 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3175 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCCUCGAACUUCACCUCG CGAGGUGAAGUUCGAGGGC -2.4 -3.40 -1.40 1.00 0.00 4.00 -42.3 44.70 5.40 1.00 II 63.20 42.00 40.11 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3176 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCCCUCGAACUUCACCUC GAGGUGAAGUUCGAGGGCG -2.4 -2.40 -1.00 0.00 -1.00 5.00 -42.3 50.60 6.10 -1.00 II 63.20 39.70 58.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3177 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGCCCUCGAACUUCACCU AGGUGAAGUUCGAGGGCGA -2.1 -2.40 -1.00 3.00 2.00 5.00 -42.3 68.30 -1.70 3.00 II 57.90 63.60 76.05 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3178 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGCCCUCGAACUUCACC GGUGAAGUUCGAGGGCGAC -3.3 -2.20 -1.00 1.00 2.00 5.00 -42.4 56.30 14.40 -1.00 II 63.20 47.70 68.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3179 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUCGCCCUCGAACUUCAC GUGAAGUUCGAGGGCGACA -2.2 -2.10 -1.00 1.00 3.00 5.00 -41.2 53.70 4.80 2.00 II 57.90 52.80 68.96 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3180 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGUCGCCCUCGAACUUCA UGAAGUUCGAGGGCGACAC -2.1 -2.20 -1.00 1.00 -2.00 5.00 -41.2 47.90 -8.70 1.00 III 57.90 36.50 66.49 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3181 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGUCGCCCUCGAACUUC GAAGUUCGAGGGCGACACC -2.4 -3.30 -1.00 1.00 0.00 5.00 -42.4 40.40 5.10 2.00 II 63.20 42.40 51.84 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3182 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUGUCGCCCUCGAACUU AAGUUCGAGGGCGACACCC -0.9 -3.30 -2.30 0.00 -2.00 5.00 -43.3 36.00 -0.90 -1.00 III 63.20 24.10 38.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3183 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGGUGUCGCCCUCGAACU AGUUCGAGGGCGACACCCU -2.1 -2.10 -4.10 3.00 0.00 5.00 -44.5 49.20 -8.70 2.00 II 63.20 51.60 53.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3184 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGGUGUCGCCCUCGAAC GUUCGAGGGCGACACCCUG -2.2 -2.10 -4.80 0.00 0.00 5.00 -44.5 44.60 5.40 0.00 II 68.40 47.40 58.99 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3185 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAGGGUGUCGCCCUCGAA UUCGAGGGCGACACCCUGG -0.9 -3.30 -4.80 0.00 -3.00 5.00 -45.6 27.10 -5.70 0.00 III 68.40 25.60 26.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3186 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACCAGGGUGUCGCCCUCGA UCGAGGGCGACACCCUGGU -2.4 -2.20 -4.80 2.00 0.00 5.00 -46.9 32.50 -3.70 2.00 II 68.40 35.90 32.61 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3187 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACCAGGGUGUCGCCCUCG CGAGGGCGACACCCUGGUG -2.4 -2.10 -4.80 0.00 0.00 5.00 -46.6 28.20 -1.70 2.00 II 73.70 49.00 25.29 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3188 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCACCAGGGUGUCGCCCUC GAGGGCGACACCCUGGUGA -2.4 -2.40 -4.80 1.00 3.00 5.00 -46.6 38.70 12.80 3.00 II 68.40 51.40 39.28 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3189 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCACCAGGGUGUCGCCCU AGGGCGACACCCUGGUGAA -2.1 -0.90 -4.40 1.00 2.00 5.00 -45.1 58.00 -4.00 4.00 II 63.20 63.90 55.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3190 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUCACCAGGGUGUCGCCC GGGCGACACCCUGGUGAAC -3.3 -2.20 -3.30 2.00 4.00 5.00 -45.2 44.80 15.50 1.00 II 68.40 46.70 44.30 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3191 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUUCACCAGGGUGUCGCC GGCGACACCCUGGUGAACC -3.3 -3.30 -3.20 -1.00 2.00 4.00 -45.2 44.00 7.40 0.00 II 68.40 33.20 62.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3192 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGUUCACCAGGGUGUCGC GCGACACCCUGGUGAACCG -3.4 -2.40 -3.20 0.00 1.00 3.00 -44.3 53.20 7.70 2.00 II 68.40 47.90 80.95 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3193 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGUUCACCAGGGUGUCG CGACACCCUGGUGAACCGC -2.4 -3.40 -3.20 0.00 0.00 4.00 -44.3 34.70 2.30 0.00 II 68.40 34.80 38.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3194 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCGGUUCACCAGGGUGUC GACACCCUGGUGAACCGCA -2.4 -2.10 -3.20 0.00 2.00 4.00 -44 43.60 5.10 2.00 II 63.20 53.40 51.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3195 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGCGGUUCACCAGGGUGU ACACCCUGGUGAACCGCAU -2.2 -1.10 -3.20 3.00 1.00 4.00 -42.7 49.50 -11.30 4.00 II 57.90 55.10 75.63 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3196 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGCGGUUCACCAGGGUG CACCCUGGUGAACCGCAUC -2.1 -2.40 -2.80 0.00 2.00 4.00 -42.9 46.30 2.40 1.00 II 63.20 44.20 66.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3197 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAUGCGGUUCACCAGGGU ACCCUGGUGAACCGCAUCG -2.2 -2.40 -2.80 -1.00 -1.00 4.00 -43.2 33.10 -5.90 1.00 III 63.20 31.40 50.81 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3198 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGAUGCGGUUCACCAGGG CCCUGGUGAACCGCAUCGA -3.3 -2.40 -2.80 1.00 3.00 4.00 -43.4 44.10 -4.90 3.00 II 63.20 59.10 82.86 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3199 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGAUGCGGUUCACCAGG CCUGGUGAACCGCAUCGAG -3.3 -2.10 -2.80 0.00 0.00 4.00 -42.2 44.10 6.10 1.00 II 63.20 52.40 64.13 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3200 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUCGAUGCGGUUCACCAG CUGGUGAACCGCAUCGAGC -2.1 -3.40 -2.80 3.00 1.00 4.00 -42.3 44.20 3.00 0.00 II 63.20 34.90 55.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3201 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUCGAUGCGGUUCACCA UGGUGAACCGCAUCGAGCU -2.1 -2.10 -2.80 2.00 1.00 4.00 -42.3 59.60 -1.40 2.00 II 57.90 46.90 61.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3202 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCUCGAUGCGGUUCACC GGUGAACCGCAUCGAGCUG -3.3 -2.10 -2.80 0.00 1.00 4.00 -42.3 46.40 5.40 1.00 II 63.20 51.70 57.74 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3203 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCAGCUCGAUGCGGUUCAC GUGAACCGCAUCGAGCUGA -2.2 -2.40 -0.80 -1.00 3.00 4.00 -41.4 48.10 5.10 3.00 II 57.90 48.10 71.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3204 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCAGCUCGAUGCGGUUCA UGAACCGCAUCGAGCUGAA -2.1 -0.90 -0.80 1.00 0.00 4.00 -40.1 64.10 -1.40 8.00 II 52.60 59.90 77.65 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3205 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUCAGCUCGAUGCGGUUC GAACCGCAUCGAGCUGAAG -2.4 -2.10 -0.80 1.00 0.00 4.00 -40.1 55.60 13.40 3.00 II 57.90 48.70 69.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3206 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUUCAGCUCGAUGCGGUU AACCGCAUCGAGCUGAAGG -0.9 -3.30 -0.80 -2.00 -2.00 4.00 -41 43.30 -6.00 2.00 III 57.90 28.50 52.52 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3207 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCUUCAGCUCGAUGCGGU ACCGCAUCGAGCUGAAGGG -2.2 -3.30 -0.80 0.00 -1.00 4.00 -43.4 45.20 -8.60 2.00 III 63.20 34.10 70.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3208 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCCUUCAGCUCGAUGCGG CCGCAUCGAGCUGAAGGGC -3.3 -3.40 -0.80 2.00 1.00 4.00 -44.6 29.50 -2.40 0.00 II 68.40 34.30 37.51 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3209 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCCUUCAGCUCGAUGCG CGCAUCGAGCUGAAGGGCA -2.4 -2.10 -2.10 1.00 3.00 4.00 -43.4 56.90 3.10 2.00 II 63.20 57.20 80.91 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3210 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGCCCUUCAGCUCGAUGC GCAUCGAGCUGAAGGGCAU -3.4 -1.10 -2.10 4.00 3.00 4.00 -42.1 75.60 5.10 4.00 II 57.90 68.20 83.65 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3211 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGCCCUUCAGCUCGAUG CAUCGAGCUGAAGGGCAUC -2.1 -2.40 -2.10 0.00 2.00 4.00 -41.1 59.80 7.00 0.00 II 57.90 42.70 72.67 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3212 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAUGCCCUUCAGCUCGAU AUCGAGCUGAAGGGCAUCG -1.1 -2.40 -2.10 -1.00 -2.00 4.00 -41.4 36.80 -8.30 0.00 III 57.90 25.10 46.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3213 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGAUGCCCUUCAGCUCGA UCGAGCUGAAGGGCAUCGA -2.4 -2.40 -2.10 0.00 0.00 4.00 -42.7 43.20 -8.70 3.00 II 57.90 47.10 52.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3214 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGAUGCCCUUCAGCUCG CGAGCUGAAGGGCAUCGAC -2.4 -2.20 -2.10 1.00 1.00 4.00 -42.5 50.40 8.10 2.00 II 63.20 52.40 65.53 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3215 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUCGAUGCCCUUCAGCUC GAGCUGAAGGGCAUCGACU -2.4 -2.10 -2.10 4.00 3.00 4.00 -42.2 54.90 8.10 2.00 Ib 57.90 52.60 60.50 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3216 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AAGUCGAUGCCCUUCAGCU AGCUGAAGGGCAUCGACUU -2.1 -0.90 -2.10 2.00 3.00 4.00 -40.7 67.10 -6.30 4.00 II 52.60 59.20 80.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3217 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAAGUCGAUGCCCUUCAGC GCUGAAGGGCAUCGACUUC -3.4 -2.40 -2.20 0.00 3.00 4.00 -41 53.40 7.40 2.00 II 57.90 52.00 66.55 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3218 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAAGUCGAUGCCCUUCAG CUGAAGGGCAUCGACUUCA -2.1 -2.10 -3.90 0.00 3.00 4.00 -39.7 61.50 0.10 4.00 Ib 52.60 53.80 74.36 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3219 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGAAGUCGAUGCCCUUCA UGAAGGGCAUCGACUUCAA -2.1 -0.90 -4.60 2.00 0.00 4.00 -38.5 70.20 1.40 8.00 II 47.40 68.90 64.04 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3220 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGAAGUCGAUGCCCUUC GAAGGGCAUCGACUUCAAG -2.4 -2.10 -3.90 0.00 0.00 4.00 -38.5 58.70 13.40 4.00 II 52.60 53.80 59.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3221 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUUGAAGUCGAUGCCCUU AAGGGCAUCGACUUCAAGG -0.9 -3.30 -0.40 -2.00 -2.00 4.00 -39.4 43.10 -6.00 3.00 II 52.60 32.70 43.18 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3222 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCUUGAAGUCGAUGCCCU AGGGCAUCGACUUCAAGGA -2.1 -2.40 -0.40 1.00 2.00 4.00 -40.9 58.50 -6.60 6.00 II 52.60 57.80 79.95 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3223 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCCUUGAAGUCGAUGCCC GGGCAUCGACUUCAAGGAG -3.3 -2.10 -0.20 0.00 1.00 4.00 -40.9 48.00 3.10 2.00 II 57.90 55.70 58.23 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3224 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUCCUUGAAGUCGAUGCC GGCAUCGACUUCAAGGAGG -3.3 -3.30 -1.30 0.00 1.00 3.00 -40.9 58.10 10.80 1.00 II 57.90 46.00 83.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3225 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCUCCUUGAAGUCGAUGC GCAUCGACUUCAAGGAGGA -3.4 -2.40 -1.30 2.00 2.00 2.00 -40 83.40 9.70 6.00 II 52.60 67.50 91.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3226 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCCUCCUUGAAGUCGAUG CAUCGACUUCAAGGAGGAC -2.1 -2.20 -1.30 1.00 1.00 2.00 -38.8 56.20 4.60 1.00 II 52.60 43.70 51.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3227 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCCUCCUUGAAGUCGAU AUCGACUUCAAGGAGGACG -1.1 -2.40 -1.30 -1.00 -2.00 2.00 -39.1 43.40 -8.60 0.00 III 52.60 24.30 19.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3228 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUCCUCCUUGAAGUCGA UCGACUUCAAGGAGGACGG -2.4 -3.30 -1.30 1.00 -3.00 3.00 -41.3 47.20 -8.30 0.00 III 57.90 34.60 44.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3229 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUCCUCCUUGAAGUCG CGACUUCAAGGAGGACGGC -2.4 -3.40 -1.30 1.00 0.00 4.00 -42.3 43.10 3.00 0.00 II 63.20 38.70 42.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3230 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCGUCCUCCUUGAAGUC GACUUCAAGGAGGACGGCA -2.4 -2.10 -1.30 0.00 2.00 4.00 -42 53.10 8.10 1.00 II 57.90 51.80 53.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3231 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGCCGUCCUCCUUGAAGU ACUUCAAGGAGGACGGCAA -2.2 -0.90 -1.30 3.00 2.00 4.00 -40.5 70.90 -6.30 4.00 II 52.60 64.20 86.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3232 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGCCGUCCUCCUUGAAG CUUCAAGGAGGACGGCAAC -2.1 -2.20 -0.80 1.00 2.00 4.00 -40.5 58.70 2.40 2.00 II 57.90 44.10 62.85 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3233 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUUGCCGUCCUCCUUGAA UUCAAGGAGGACGGCAACA -0.9 -2.10 1.30 0.00 0.00 4.00 -40.5 60.40 -0.70 5.00 II 52.60 38.30 68.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3234 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGUUGCCGUCCUCCUUGA UCAAGGAGGACGGCAACAU -2.4 -1.10 1.60 2.00 0.00 4.00 -40.7 61.20 -8.50 6.00 II 52.60 47.00 90.74 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3235 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGUUGCCGUCCUCCUUG CAAGGAGGACGGCAACAUC -2.1 -2.40 3.10 1.00 2.00 4.00 -40.7 60.10 2.40 4.00 II 57.90 53.90 71.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3236 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGAUGUUGCCGUCCUCCUU AAGGAGGACGGCAACAUCC -0.9 -3.30 -0.40 2.00 -1.00 4.00 -41.9 55.20 1.50 2.00 II 57.90 36.50 30.98 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3237 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGAUGUUGCCGUCCUCCU AGGAGGACGGCAACAUCCU -2.1 -2.10 -2.20 3.00 1.00 4.00 -43.1 58.90 -6.30 3.00 II 57.90 53.70 68.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3238 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGAUGUUGCCGUCCUCC GGAGGACGGCAACAUCCUG -3.3 -2.10 -2.90 -1.00 1.00 4.00 -43.1 49.50 5.70 2.00 II 63.20 57.60 40.72 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3239 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAGGAUGUUGCCGUCCUC GAGGACGGCAACAUCCUGG -2.4 -3.30 -2.90 -1.00 0.00 4.00 -43.1 33.70 5.50 0.00 II 63.20 38.10 15.23 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3240 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCAGGAUGUUGCCGUCCU AGGACGGCAACAUCCUGGG -2.1 -3.30 -2.50 0.00 -2.00 4.00 -44 38.70 -3.60 0.00 III 63.20 36.80 80.61 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3241 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCCAGGAUGUUGCCGUCC GGACGGCAACAUCCUGGGG -3.3 -3.30 -1.40 0.00 -1.00 4.00 -45.2 33.10 11.10 1.00 II 68.40 45.00 81.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3242 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCCCAGGAUGUUGCCGUC GACGGCAACAUCCUGGGGC -2.4 -3.40 -0.10 0.00 0.00 5.00 -45.3 33.80 10.40 0.00 II 68.40 26.50 28.24 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3243 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCCCAGGAUGUUGCCGU ACGGCAACAUCCUGGGGCA -2.2 -2.10 -0.10 2.00 2.00 5.00 -45 55.00 -1.60 4.00 II 63.20 55.00 84.16 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3244 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGCCCCAGGAUGUUGCCG CGGCAACAUCCUGGGGCAC -2.4 -2.20 0.10 2.00 3.00 5.00 -45 45.20 7.70 0.00 II 68.40 42.90 55.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3245 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUGCCCCAGGAUGUUGCC GGCAACAUCCUGGGGCACA -3.3 -2.10 0.10 -1.00 4.00 5.00 -44.7 55.60 7.40 3.00 II 63.20 55.40 68.58 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3246 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUGCCCCAGGAUGUUGC GCAACAUCCUGGGGCACAA -3.4 -0.90 0.10 1.00 4.00 5.00 -42.3 72.20 7.10 6.00 II 57.90 69.40 84.43 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3247 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGUGCCCCAGGAUGUUG CAACAUCCUGGGGCACAAG -2.1 -2.10 0.70 0.00 0.00 5.00 -41 50.90 0.30 3.00 II 57.90 47.10 76.97 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3248 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUUGUGCCCCAGGAUGUU AACAUCCUGGGGCACAAGC -0.9 -3.40 0.70 0.00 -1.00 5.00 -42.3 34.20 -6.30 2.00 III 57.90 25.70 39.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3249 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUUGUGCCCCAGGAUGU ACAUCCUGGGGCACAAGCU -2.2 -2.10 -1.30 2.00 0.00 5.00 -43.5 51.00 -11.30 4.00 II 57.90 45.90 55.51 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3250 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCUUGUGCCCCAGGAUG CAUCCUGGGGCACAAGCUG -2.1 -2.10 -2.00 1.00 -1.00 5.00 -43.4 45.90 -4.30 1.00 II 63.20 47.30 45.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3251 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAGCUUGUGCCCCAGGAU AUCCUGGGGCACAAGCUGG -1.1 -3.30 -2.00 0.00 -2.00 5.00 -44.6 38.60 -8.30 0.00 III 63.20 32.90 32.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3252 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCAGCUUGUGCCCCAGGA UCCUGGGGCACAAGCUGGA -2.4 -2.40 -2.00 2.00 0.00 5.00 -45.9 51.70 -3.70 3.00 II 63.20 47.20 64.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3253 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCCAGCUUGUGCCCCAGG CCUGGGGCACAAGCUGGAG -3.3 -2.10 -2.00 0.00 0.00 5.00 -45.6 36.90 3.10 0.00 II 68.40 45.50 26.71 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3254 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUCCAGCUUGUGCCCCAG CUGGGGCACAAGCUGGAGU -2.1 -2.20 -2.00 2.00 3.00 5.00 -44.5 44.30 3.00 2.00 II 63.20 43.30 90.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3255 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UACUCCAGCUUGUGCCCCA UGGGGCACAAGCUGGAGUA -2.1 -1.30 -2.00 0.00 1.00 5.00 -43.7 58.00 -3.80 4.00 II 57.90 55.20 64.89 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3256 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUACUCCAGCUUGUGCCCC GGGGCACAAGCUGGAGUAC -3.3 -2.20 -2.00 2.00 4.00 5.00 -43.8 47.70 12.80 1.00 II 63.20 50.50 50.80 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3257 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUACUCCAGCUUGUGCCC GGGCACAAGCUGGAGUACA -3.3 -2.10 -2.00 -1.00 4.00 4.00 -42.6 68.80 8.10 3.00 Ib 57.90 62.20 88.84 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3258 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUACUCCAGCUUGUGCC GGCACAAGCUGGAGUACAA -3.3 -0.90 -1.60 2.00 5.00 3.00 -40.2 86.50 10.10 7.00 Ia 52.60 79.00 89.95 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3259 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGUACUCCAGCUUGUGC GCACAAGCUGGAGUACAAC -3.4 -2.20 -0.50 1.00 3.00 2.00 -39.1 67.50 14.40 4.00 II 52.60 48.30 85.91 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3260 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUUGUACUCCAGCUUGUG CACAAGCUGGAGUACAACU -2.1 -2.10 0.70 1.00 3.00 2.00 -37.8 61.30 -2.40 5.00 Ia 47.40 54.10 73.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3261 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGUUGUACUCCAGCUUGU ACAAGCUGGAGUACAACUA -2.2 -1.30 0.70 1.00 1.00 2.00 -37 72.00 -11.30 8.00 II 42.10 63.30 77.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3262 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGUUGUACUCCAGCUUG CAAGCUGGAGUACAACUAC -2.1 -2.20 0.70 0.00 1.00 2.00 -37 61.70 0.10 5.00 II 47.40 55.00 77.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3263 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUAGUUGUACUCCAGCUU AAGCUGGAGUACAACUACA -0.9 -2.10 0.00 1.00 1.00 2.00 -37 76.20 -0.90 7.00 II 42.10 62.10 74.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3264 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUAGUUGUACUCCAGCU AGCUGGAGUACAACUACAA -2.1 -0.90 0.00 2.00 2.00 2.00 -37 79.90 -1.30 7.00 II 42.10 69.90 81.59 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3265 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGUAGUUGUACUCCAGC GCUGGAGUACAACUACAAC -3.4 -2.20 0.00 0.00 3.00 2.00 -37.1 61.70 12.10 4.00 II 47.40 56.30 69.99 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3266 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUUGUAGUUGUACUCCAG CUGGAGUACAACUACAACA -2.1 -2.10 0.00 0.00 3.00 2.00 -35.8 76.30 0.40 6.00 Ia 42.10 61.80 76.29 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3267 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGUUGUAGUUGUACUCCA UGGAGUACAACUACAACAG -2.1 -2.10 0.00 1.00 -2.00 2.00 -35.8 64.60 -5.80 4.00 II 42.10 49.50 56.26 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3268 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUGUUGUAGUUGUACUCC GGAGUACAACUACAACAGC -3.3 -3.40 0.00 0.00 2.00 2.00 -37.1 64.90 12.80 4.00 II 47.40 52.30 74.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3269 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCUGUUGUAGUUGUACUC GAGUACAACUACAACAGCC -2.4 -3.30 0.00 0.00 0.00 3.00 -37.1 69.30 10.40 3.00 II 47.40 44.60 85.32 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3270 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGCUGUUGUAGUUGUACU AGUACAACUACAACAGCCA -2.1 -2.10 0.00 3.00 1.00 3.00 -36.8 79.10 0.70 5.00 II 42.10 61.10 81.16 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3271 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGCUGUUGUAGUUGUAC GUACAACUACAACAGCCAC -2.2 -2.20 0.20 0.00 1.00 3.00 -36.9 61.20 9.70 3.00 II 47.40 49.20 75.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3272 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUGGCUGUUGUAGUUGUA UACAACUACAACAGCCACA -1.3 -2.10 2.30 0.00 0.00 3.00 -36.8 62.90 -3.30 5.00 II 42.10 45.90 69.22 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3273 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUGGCUGUUGUAGUUGU ACAACUACAACAGCCACAA -2.2 -0.90 2.30 1.00 1.00 3.00 -36.4 70.80 -4.00 6.00 II 42.10 59.80 70.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3274 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGUGGCUGUUGUAGUUG CAACUACAACAGCCACAAC -2.1 -2.20 2.30 0.00 2.00 3.00 -36.4 60.50 5.40 5.00 II 47.40 51.80 68.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3275 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUUGUGGCUGUUGUAGUU AACUACAACAGCCACAACG -0.9 -2.40 2.30 -1.00 -2.00 3.00 -36.7 60.20 -3.00 3.00 III 47.40 33.00 68.52 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3276 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGUUGUGGCUGUUGUAGU ACUACAACAGCCACAACGU -2.2 -2.20 2.20 3.00 1.00 3.00 -38 65.70 -1.60 5.00 II 47.40 50.50 91.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3277 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GACGUUGUGGCUGUUGUAG CUACAACAGCCACAACGUC -2.1 -2.40 2.10 1.00 1.00 3.00 -38.2 61.40 3.00 4.00 II 52.60 43.10 85.53 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3278 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGACGUUGUGGCUGUUGUA UACAACAGCCACAACGUCU -1.3 -2.10 2.10 2.00 0.00 3.00 -38.2 54.00 -6.10 4.00 II 47.40 41.70 79.31 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3279 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGACGUUGUGGCUGUUGU ACAACAGCCACAACGUCUA -2.2 -1.30 2.10 2.00 2.00 3.00 -38.2 79.40 0.80 7.00 II 47.40 62.20 91.91 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3280 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUAGACGUUGUGGCUGUUG CAACAGCCACAACGUCUAU -2.1 -1.10 2.10 1.00 3.00 3.00 -37.1 58.60 2.70 7.00 Ib 47.40 62.80 78.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3281 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAUAGACGUUGUGGCUGUU AACAGCCACAACGUCUAUA -0.9 -1.30 2.10 -1.00 2.00 3.00 -36.3 61.60 -1.00 6.00 II 42.10 49.50 73.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3282 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUAUAGACGUUGUGGCUGU ACAGCCACAACGUCUAUAU -2.2 -1.10 2.10 1.00 2.00 3.00 -36.5 62.30 -1.30 8.00 II 42.10 56.50 74.34 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3283 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUAUAGACGUUGUGGCUG CAGCCACAACGUCUAUAUC -2.1 -2.40 2.10 1.00 3.00 3.00 -36.7 62.60 5.40 5.00 II 47.40 51.10 71.99 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3284 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAUAUAGACGUUGUGGCU AGCCACAACGUCUAUAUCA -2.1 -2.10 2.10 -1.00 2.00 3.00 -36.7 73.20 1.80 7.00 II 42.10 58.40 75.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3285 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGAUAUAGACGUUGUGGC GCCACAACGUCUAUAUCAU -3.4 -1.10 2.40 3.00 5.00 3.00 -35.7 80.70 7.40 7.00 Ia 42.10 69.20 96.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3286 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAUGAUAUAGACGUUGUGG CCACAACGUCUAUAUCAUG -3.3 -2.10 2.50 -1.00 2.00 2.00 -34.4 73.00 3.00 5.00 II 42.10 57.90 87.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3287 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAUGAUAUAGACGUUGUG CACAACGUCUAUAUCAUGG -2.1 -3.30 1.20 -1.00 0.00 2.00 -34.4 57.30 0.40 4.00 II 42.10 43.40 64.59 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3288 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCAUGAUAUAGACGUUGU ACAACGUCUAUAUCAUGGC -2.2 -3.40 -0.70 0.00 -2.00 3.00 -35.7 63.80 -4.30 4.00 III 42.10 37.50 27.48 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3289 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCCAUGAUAUAGACGUUG CAACGUCUAUAUCAUGGCC -2.1 -3.30 -1.50 1.00 -1.00 4.00 -36.8 47.30 2.70 3.00 II 47.40 45.00 53.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3290 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGCCAUGAUAUAGACGUU AACGUCUAUAUCAUGGCCG -0.9 -2.40 -1.50 0.00 -3.00 5.00 -37.1 46.00 -3.20 0.00 III 47.40 28.90 33.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3291 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGGCCAUGAUAUAGACGU ACGUCUAUAUCAUGGCCGA -2.2 -2.40 -1.50 1.00 1.00 5.00 -38.6 62.90 -4.00 4.00 II 47.40 62.80 68.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3292 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGGCCAUGAUAUAGACG CGUCUAUAUCAUGGCCGAC -2.4 -2.20 -1.50 0.00 2.00 5.00 -38.6 54.90 5.10 0.00 II 52.60 47.50 55.55 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3293 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUCGGCCAUGAUAUAGAC GUCUAUAUCAUGGCCGACA -2.2 -2.10 -1.20 1.00 3.00 5.00 -38.3 60.60 7.40 3.00 II 47.40 53.90 43.75 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3294 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUCGGCCAUGAUAUAGA UCUAUAUCAUGGCCGACAA -2.4 -0.90 0.50 1.00 1.00 5.00 -37 71.70 -4.00 7.00 II 42.10 64.10 69.70 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3295 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGUCGGCCAUGAUAUAG CUAUAUCAUGGCCGACAAG -2.1 -2.10 0.50 0.00 0.00 5.00 -36.7 64.90 3.30 5.00 II 47.40 49.70 60.50 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3296 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUUGUCGGCCAUGAUAUA UAUAUCAUGGCCGACAAGC -1.3 -3.40 0.50 0.00 -3.00 5.00 -38 43.80 -6.10 2.00 III 47.40 20.90 34.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3297 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCUUGUCGGCCAUGAUAU AUAUCAUGGCCGACAAGCA -1.1 -2.10 -0.70 2.00 0.00 5.00 -38.8 70.90 -8.90 7.00 II 47.40 55.80 85.53 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3298 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGCUUGUCGGCCAUGAUA UAUCAUGGCCGACAAGCAG -1.3 -2.10 -0.70 1.00 -4.00 5.00 -39.8 54.10 -5.70 3.00 III 52.60 41.00 61.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3299 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCUGCUUGUCGGCCAUGAU AUCAUGGCCGACAAGCAGA -1.1 -2.40 -0.70 1.00 1.00 5.00 -40.9 62.10 -1.60 5.00 II 52.60 48.50 66.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3300 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCUGCUUGUCGGCCAUGA UCAUGGCCGACAAGCAGAA -2.4 -0.90 -0.70 2.00 0.00 5.00 -40.7 63.90 -6.10 7.00 II 52.60 55.70 72.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3301 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUCUGCUUGUCGGCCAUG CAUGGCCGACAAGCAGAAG -2.1 -2.10 -0.70 -1.00 0.00 5.00 -40.4 42.20 -4.40 2.00 II 57.90 46.00 38.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3302 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCUUCUGCUUGUCGGCCAU AUGGCCGACAAGCAGAAGA -1.1 -2.40 -0.70 -1.00 1.00 5.00 -40.7 64.40 1.50 6.00 II 52.60 46.00 62.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3303 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCUUCUGCUUGUCGGCCA UGGCCGACAAGCAGAAGAA -2.1 -0.90 -0.70 2.00 1.00 5.00 -40.5 72.40 -3.80 7.00 II 52.60 61.50 82.16 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3304 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUCUUCUGCUUGUCGGCC GGCCGACAAGCAGAAGAAC -3.3 -2.20 -0.70 2.00 4.00 5.00 -40.6 59.90 12.80 2.00 II 57.90 52.20 63.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3305 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUUCUUCUGCUUGUCGGC GCCGACAAGCAGAAGAACG -3.4 -2.40 -0.70 -1.00 1.00 4.00 -39.7 64.90 6.10 2.00 II 57.90 46.70 90.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3306 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUUCUUCUGCUUGUCGG CCGACAAGCAGAAGAACGG -3.3 -3.30 0.00 1.00 1.00 3.00 -39.6 69.00 -2.00 2.00 II 57.90 47.00 83.89 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3307 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUUCUUCUGCUUGUCG CGACAAGCAGAAGAACGGC -2.4 -3.40 1.40 0.00 1.00 4.00 -39.7 56.50 4.70 1.00 II 57.90 42.20 76.05 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3308 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCGUUCUUCUGCUUGUC GACAAGCAGAAGAACGGCA -2.4 -2.10 -0.30 2.00 2.00 4.00 -39.4 64.50 8.10 4.00 II 52.60 58.10 84.26 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3309 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGCCGUUCUUCUGCUUGU ACAAGCAGAAGAACGGCAU -2.2 -1.10 -0.30 3.00 1.00 4.00 -38.1 65.90 -6.30 5.00 II 47.40 54.90 72.88 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3310 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGCCGUUCUUCUGCUUG CAAGCAGAAGAACGGCAUC -2.1 -2.40 -0.30 0.00 2.00 4.00 -38.3 67.30 7.80 4.00 II 52.60 48.80 72.26 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3311 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAUGCCGUUCUUCUGCUU AAGCAGAAGAACGGCAUCA -0.9 -2.10 -0.30 0.00 1.00 4.00 -38.3 66.50 -3.30 5.00 II 47.40 49.90 78.94 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3312 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGAUGCCGUUCUUCUGCU AGCAGAAGAACGGCAUCAA -2.1 -0.90 -0.30 1.00 3.00 4.00 -38.3 71.80 -4.00 6.00 II 47.40 65.20 73.19 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3313 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGAUGCCGUUCUUCUGC GCAGAAGAACGGCAUCAAG -3.4 -2.10 -0.10 0.00 2.00 4.00 -38.3 67.90 15.90 5.00 II 52.60 59.80 62.15 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3314 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUUGAUGCCGUUCUUCUG CAGAAGAACGGCAUCAAGG -2.1 -3.30 0.80 1.00 0.00 4.00 -38.2 64.70 1.00 3.00 II 52.60 42.80 73.29 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3315 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACCUUGAUGCCGUUCUUCU AGAAGAACGGCAUCAAGGU -2.1 -2.20 0.80 2.00 1.00 4.00 -38.3 71.50 -4.00 6.00 II 47.40 52.80 82.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3316 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACCUUGAUGCCGUUCUUC GAAGAACGGCAUCAAGGUG -2.4 -2.10 0.20 0.00 0.00 4.00 -38.3 58.50 3.00 4.00 II 52.60 51.20 68.43 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3317 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCACCUUGAUGCCGUUCUU AAGAACGGCAUCAAGGUGA -0.9 -2.40 -0.90 1.00 1.00 4.00 -38.3 62.50 -3.90 5.00 II 47.40 50.30 70.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3318 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCACCUUGAUGCCGUUCU AGAACGGCAUCAAGGUGAA -2.1 -0.90 -0.90 2.00 1.00 4.00 -38.3 82.90 -1.60 8.00 II 47.40 69.30 91.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3319 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUCACCUUGAUGCCGUUC GAACGGCAUCAAGGUGAAC -2.4 -2.20 -0.90 1.00 1.00 4.00 -38.4 61.30 15.40 4.00 II 52.60 46.90 74.28 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3320 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUUCACCUUGAUGCCGUU AACGGCAUCAAGGUGAACU -0.9 -2.10 -0.90 0.00 1.00 4.00 -38.1 56.70 -4.00 4.00 II 47.40 37.10 59.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3321 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AAGUUCACCUUGAUGCCGU ACGGCAUCAAGGUGAACUU -2.2 -0.90 -0.90 2.00 3.00 4.00 -38.1 67.70 -4.20 6.00 II 47.40 58.90 87.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3322 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAAGUUCACCUUGAUGCCG CGGCAUCAAGGUGAACUUC -2.4 -2.40 -0.90 1.00 3.00 4.00 -38.3 54.00 3.00 3.00 II 52.60 53.40 70.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3323 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAAGUUCACCUUGAUGCC GGCAUCAAGGUGAACUUCA -3.3 -2.10 -0.90 0.00 4.00 3.00 -38 72.80 8.10 6.00 Ia 47.40 68.20 94.06 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3324 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGAAGUUCACCUUGAUGC GCAUCAAGGUGAACUUCAA -3.4 -0.90 -0.90 2.00 4.00 2.00 -35.6 91.40 7.70 9.00 Ia 42.10 83.90 90.63 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3325 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGAAGUUCACCUUGAUG CAUCAAGGUGAACUUCAAG -2.1 -2.10 -0.70 -1.00 1.00 2.00 -34.3 67.60 5.40 4.00 II 42.10 51.90 85.50 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3326 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCUUGAAGUUCACCUUGAU AUCAAGGUGAACUUCAAGA -1.1 -2.40 -0.40 0.00 1.00 2.00 -34.6 66.40 -3.90 6.00 II 36.80 47.80 77.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3327 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUCUUGAAGUUCACCUUGA UCAAGGUGAACUUCAAGAU -2.4 -1.10 -0.40 2.00 0.00 2.00 -34.6 69.10 -8.70 7.00 II 36.80 55.40 96.03 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3328 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUCUUGAAGUUCACCUUG CAAGGUGAACUUCAAGAUC -2.1 -2.40 -0.40 1.00 1.00 2.00 -34.6 68.40 5.40 5.00 II 42.10 54.10 93.71 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3329 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGAUCUUGAAGUUCACCUU AAGGUGAACUUCAAGAUCC -0.9 -3.30 -0.40 1.00 -1.00 2.00 -35.8 74.40 -1.00 4.00 II 42.10 42.50 93.86 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3330 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGAUCUUGAAGUUCACCU AGGUGAACUUCAAGAUCCG -2.1 -2.40 -0.10 1.00 -1.00 3.00 -37.3 75.10 -1.30 4.00 III 47.40 52.40 93.27 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3331 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGAUCUUGAAGUUCACC GGUGAACUUCAAGAUCCGC -3.3 -3.40 0.30 0.00 1.00 4.00 -38.6 51.00 14.70 1.00 II 52.60 45.50 72.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3332 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCGGAUCUUGAAGUUCAC GUGAACUUCAAGAUCCGCC -2.2 -3.30 0.50 0.00 0.00 5.00 -38.6 41.70 4.80 1.00 II 52.60 31.50 56.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3333 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGCGGAUCUUGAAGUUCA UGAACUUCAAGAUCCGCCA -2.1 -2.10 1.10 2.00 -1.00 5.00 -38.5 55.00 -6.30 5.00 II 47.40 56.70 78.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3334 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGCGGAUCUUGAAGUUC GAACUUCAAGAUCCGCCAC -2.4 -2.20 1.80 0.00 0.00 5.00 -38.6 46.70 10.40 3.00 II 52.60 47.80 75.05 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3335 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUGGCGGAUCUUGAAGUU AACUUCAAGAUCCGCCACA -0.9 -2.10 2.30 -1.00 1.00 5.00 -38.3 55.30 -3.30 5.00 II 47.40 46.40 65.81 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3336 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUGGCGGAUCUUGAAGU ACUUCAAGAUCCGCCACAA -2.2 -0.90 2.30 1.00 2.00 5.00 -38.3 68.40 -4.00 6.00 II 47.40 64.20 84.53 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3337 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGUGGCGGAUCUUGAAG CUUCAAGAUCCGCCACAAC -2.1 -2.20 2.80 1.00 2.00 5.00 -38.3 62.00 10.10 4.00 II 52.60 45.90 69.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3338 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUUGUGGCGGAUCUUGAA UUCAAGAUCCGCCACAACA -0.9 -2.10 4.80 1.00 0.00 5.00 -38.3 65.70 -3.80 6.00 II 47.40 47.00 81.89 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3339 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGUUGUGGCGGAUCUUGA UCAAGAUCCGCCACAACAU -2.4 -1.10 5.40 3.00 1.00 5.00 -38.5 67.80 -4.00 7.00 II 47.40 54.20 80.01 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3340 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGUUGUGGCGGAUCUUG CAAGAUCCGCCACAACAUC -2.1 -2.40 2.70 1.00 1.00 5.00 -38.5 54.70 -2.40 5.00 II 52.60 49.00 57.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3341 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAUGUUGUGGCGGAUCUU AAGAUCCGCCACAACAUCG -0.9 -2.40 1.00 -1.00 -2.00 5.00 -38.8 44.30 -8.30 3.00 II 52.60 35.50 62.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3342 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGAUGUUGUGGCGGAUCU AGAUCCGCCACAACAUCGA -2.1 -2.40 1.00 1.00 0.00 5.00 -40.3 62.60 -1.60 7.00 II 52.60 56.10 80.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3343 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGAUGUUGUGGCGGAUC GAUCCGCCACAACAUCGAG -2.4 -2.10 1.20 -1.00 -1.00 5.00 -40.3 46.80 8.10 2.00 II 57.90 50.60 57.92 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3344 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCUCGAUGUUGUGGCGGAU AUCCGCCACAACAUCGAGG -1.1 -3.30 1.20 0.00 -2.00 5.00 -41.2 34.50 -3.00 1.00 III 57.90 22.80 36.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3345 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCUCGAUGUUGUGGCGGA UCCGCCACAACAUCGAGGA -2.4 -2.40 -0.60 0.00 0.00 5.00 -42.5 49.20 -3.80 4.00 II 57.90 43.70 77.77 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3346 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCCUCGAUGUUGUGGCGG CCGCCACAACAUCGAGGAC -3.3 -2.20 0.20 1.00 3.00 5.00 -42.3 47.10 5.40 2.00 II 63.20 46.50 29.22 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3347 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCCUCGAUGUUGUGGCG CGCCACAACAUCGAGGACG -2.4 -2.40 0.40 -1.00 1.00 4.00 -41.4 50.10 1.00 0.00 II 63.20 35.10 36.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3348 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUCCUCGAUGUUGUGGC GCCACAACAUCGAGGACGG -3.4 -3.30 0.40 1.00 1.00 3.00 -42.3 60.70 7.70 2.00 II 63.20 48.00 73.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3349 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUCCUCGAUGUUGUGG CCACAACAUCGAGGACGGC -3.3 -3.40 0.30 1.00 1.00 4.00 -42.3 53.10 7.70 1.00 II 63.20 36.60 50.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3350 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCGUCCUCGAUGUUGUG CACAACAUCGAGGACGGCA -2.1 -2.10 0.30 0.00 2.00 4.00 -41.1 51.50 0.00 2.00 II 57.90 48.40 42.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3351 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGCCGUCCUCGAUGUUGU ACAACAUCGAGGACGGCAG -2.2 -2.10 0.30 2.00 -1.00 4.00 -41.1 55.20 -8.60 2.00 III 57.90 44.40 49.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3352 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUGCCGUCCUCGAUGUUG CAACAUCGAGGACGGCAGC -2.1 -3.40 0.30 1.00 0.00 4.00 -42.3 42.50 -2.40 2.00 II 63.20 38.60 41.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3353 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCUGCCGUCCUCGAUGUU AACAUCGAGGACGGCAGCG -0.9 -2.40 0.30 -2.00 -3.00 4.00 -42.6 35.30 -2.90 0.00 III 63.20 19.50 22.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3354 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGCUGCCGUCCUCGAUGU ACAUCGAGGACGGCAGCGU -2.2 -2.20 -0.30 3.00 0.00 4.00 -43.9 43.80 -8.70 3.00 II 63.20 41.00 46.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3355 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACGCUGCCGUCCUCGAUG CAUCGAGGACGGCAGCGUG -2.1 -2.10 -1.00 0.00 0.00 4.00 -43.8 47.20 0.40 0.00 II 68.40 49.00 55.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3356 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCACGCUGCCGUCCUCGAU AUCGAGGACGGCAGCGUGC -1.1 -3.40 -1.00 3.00 -1.00 4.00 -45.1 37.10 1.50 0.00 III 68.40 25.50 29.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3357 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCACGCUGCCGUCCUCGA UCGAGGACGGCAGCGUGCA -2.4 -2.10 -1.30 1.00 0.00 4.00 -46.1 46.70 -6.10 2.00 II 68.40 43.20 37.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3358 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGCACGCUGCCGUCCUCG CGAGGACGGCAGCGUGCAG -2.4 -2.10 -1.30 0.00 1.00 4.00 -45.8 36.90 -1.70 2.00 II 73.70 51.30 27.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3359 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUGCACGCUGCCGUCCUC GAGGACGGCAGCGUGCAGC -2.4 -3.40 -1.30 0.00 1.00 4.00 -46.8 28.00 7.50 -1.00 II 73.70 26.50 20.11 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3360 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUGCACGCUGCCGUCCU AGGACGGCAGCGUGCAGCU -2.1 -2.10 -1.90 2.00 1.00 4.00 -46.5 42.80 -1.60 2.00 II 68.40 44.60 26.23 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3361 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAGCUGCACGCUGCCGUCC GGACGGCAGCGUGCAGCUC -3.3 -2.40 -2.00 2.00 1.00 4.00 -46.8 37.80 8.10 1.00 II 73.70 45.80 39.97 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3362 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAGCUGCACGCUGCCGUC GACGGCAGCGUGCAGCUCG -2.4 -2.40 -2.00 -2.00 0.00 4.00 -45.9 34.70 3.10 0.00 II 73.70 39.50 30.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3363 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGAGCUGCACGCUGCCGU ACGGCAGCGUGCAGCUCGC -2.2 -3.40 -2.00 2.00 0.00 4.00 -46.9 37.60 -1.60 1.00 III 73.70 35.30 31.53 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3364 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCGAGCUGCACGCUGCCG CGGCAGCGUGCAGCUCGCC -2.4 -3.30 -2.40 1.00 1.00 4.00 -48 23.40 2.70 -1.00 II 78.90 33.00 27.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3365 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGCGAGCUGCACGCUGCC GGCAGCGUGCAGCUCGCCG -3.3 -2.40 -3.20 -1.00 0.00 5.00 -48 16.70 5.50 -1.00 II 78.90 36.50 15.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3366 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGGCGAGCUGCACGCUGC GCAGCGUGCAGCUCGCCGA -3.4 -2.40 -2.40 1.00 2.00 5.00 -47.1 42.00 2.50 3.00 II 73.70 59.90 45.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3367 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGGCGAGCUGCACGCUG CAGCGUGCAGCUCGCCGAC -2.1 -2.20 -2.40 1.00 1.00 5.00 -45.9 25.70 2.40 0.00 II 73.70 40.30 30.52 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3368 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCGGCGAGCUGCACGCU AGCGUGCAGCUCGCCGACC -2.1 -3.30 -2.40 1.00 0.00 5.00 -47.1 20.70 -3.30 -1.00 III 73.70 25.60 36.25 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3369 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGUCGGCGAGCUGCACGC GCGUGCAGCUCGCCGACCA -3.4 -2.10 -2.20 0.00 3.00 5.00 -47.1 47.40 5.10 4.00 II 73.70 60.40 62.15 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3370 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGUCGGCGAGCUGCACG CGUGCAGCUCGCCGACCAC -2.4 -2.20 -0.10 1.00 2.00 5.00 -45.9 42.90 7.00 2.00 II 73.70 48.80 54.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3371 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUGGUCGGCGAGCUGCAC GUGCAGCUCGCCGACCACU -2.2 -2.10 -0.10 2.00 3.00 5.00 -45.6 34.60 7.40 2.00 II 68.40 42.10 56.92 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3372 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGUGGUCGGCGAGCUGCA UGCAGCUCGCCGACCACUA -2.1 -1.30 -0.10 1.00 1.00 5.00 -44.7 43.50 -8.70 5.00 II 63.20 54.90 56.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3373 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGUGGUCGGCGAGCUGC GCAGCUCGCCGACCACUAC -3.4 -2.20 -0.10 1.00 2.00 5.00 -44.8 40.60 5.10 4.00 II 68.40 52.50 51.22 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3374 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUAGUGGUCGGCGAGCUG CAGCUCGCCGACCACUACC -2.1 -3.30 2.90 -1.00 1.00 5.00 -44.7 32.70 2.40 2.00 II 68.40 33.00 49.93 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3375 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGUAGUGGUCGGCGAGCU AGCUCGCCGACCACUACCA -2.1 -2.10 3.20 2.00 1.00 5.00 -44.7 44.80 -3.60 5.00 II 63.20 52.70 64.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3376 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGGUAGUGGUCGGCGAGC GCUCGCCGACCACUACCAG -3.4 -2.10 3.20 -1.00 0.00 5.00 -44.7 30.00 3.10 2.00 II 68.40 46.70 34.38 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3377 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUGGUAGUGGUCGGCGAG CUCGCCGACCACUACCAGC -2.1 -3.40 2.00 -1.00 1.00 5.00 -44.7 34.10 5.40 1.00 II 68.40 31.50 32.31 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3378 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCUGGUAGUGGUCGGCGA UCGCCGACCACUACCAGCA -2.4 -2.10 0.30 2.00 0.00 5.00 -44.7 50.00 -3.80 4.00 II 63.20 45.50 74.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3379 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGCUGGUAGUGGUCGGCG CGCCGACCACUACCAGCAG -2.4 -2.10 0.30 0.00 2.00 5.00 -44.4 39.20 0.30 2.00 II 68.40 52.00 38.65 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3380 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCUGCUGGUAGUGGUCGGC GCCGACCACUACCAGCAGA -3.4 -2.40 0.60 -1.00 4.00 4.00 -44.4 52.60 10.40 5.00 II 63.20 59.10 58.69 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3381 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCUGCUGGUAGUGGUCGG CCGACCACUACCAGCAGAA -3.3 -0.90 1.40 1.00 4.00 3.00 -41.9 63.90 2.30 5.00 Ib 57.90 60.90 78.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3382 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUCUGCUGGUAGUGGUCG CGACCACUACCAGCAGAAC -2.4 -2.20 1.40 2.00 3.00 2.00 -40.8 51.00 2.30 3.00 II 57.90 50.20 57.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3383 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUUCUGCUGGUAGUGGUC GACCACUACCAGCAGAACA -2.4 -2.10 1.40 -1.00 3.00 2.00 -40.5 68.50 7.80 6.00 Ib 52.60 60.10 77.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3384 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGUUCUGCUGGUAGUGGU ACCACUACCAGCAGAACAC -2.2 -2.20 1.40 2.00 0.00 2.00 -40.3 64.30 -4.00 4.00 II 52.60 41.20 79.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3385 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGUUCUGCUGGUAGUGG CCACUACCAGCAGAACACC -3.3 -3.30 1.40 1.00 2.00 2.00 -41.4 50.00 2.30 2.00 II 57.90 40.30 52.61 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3386 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUGUUCUGCUGGUAGUG CACUACCAGCAGAACACCC -2.1 -3.30 1.40 0.00 0.00 3.00 -41.4 47.70 0.70 1.00 II 57.90 37.90 46.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3387 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGGUGUUCUGCUGGUAGU ACUACCAGCAGAACACCCC -2.2 -3.30 1.40 1.00 -2.00 4.00 -42.6 49.10 -6.30 1.00 III 57.90 32.20 37.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3388 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGGGUGUUCUGCUGGUAG CUACCAGCAGAACACCCCC -2.1 -3.30 1.90 0.00 0.00 5.00 -43.7 44.10 4.70 1.00 II 63.20 36.70 53.07 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3389 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGGGGUGUUCUGCUGGUA UACCAGCAGAACACCCCCA -1.3 -2.10 1.00 -1.00 5.00 -43.7 43.40 -3.10 3.00 II 57.90 44.20 64.58 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3390 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGGGGGUGUUCUGCUGGU ACCAGCAGAACACCCCCAU -2.2 -1.10 1.00 2.00 5.00 -43.5 40.80 -6.30 3.00 II 57.90 48.00 55.93 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3391 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUGGGGGUGUUCUGCUGG CCAGCAGAACACCCCCAUC -3.3 -2.40 3.50 0.00 3.00 5.00 -43.7 47.10 7.80 3.00 II 63.20 48.80 37.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3392 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAUGGGGGUGUUCUGCUG CAGCAGAACACCCCCAUCG -2.1 -2.40 1.80 0.00 0.00 5.00 -42.8 45.00 1.00 2.00 II 63.20 39.40 30.49 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3393 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGAUGGGGGUGUUCUGCU AGCAGAACACCCCCAUCGG -2.1 -3.30 0.70 0.00 -1.00 5.00 -44 42.10 -3.60 2.00 III 63.20 40.80 28.80 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3394 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGAUGGGGGUGUUCUGC GCAGAACACCCCCAUCGGC -3.4 -3.40 0.30 1.00 1.00 5.00 -45.3 39.90 15.50 2.00 II 68.40 38.40 29.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3395 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCCGAUGGGGGUGUUCUG CAGAACACCCCCAUCGGCG -2.1 -2.40 0.30 1.00 -1.00 5.00 -44.3 32.60 -2.00 0.00 II 68.40 31.30 53.10 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3396 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGCCGAUGGGGGUGUUCU AGAACACCCCCAUCGGCGA -2.1 -2.40 0.30 2.00 1.00 5.00 -44.6 51.30 -1.60 4.00 II 63.20 54.10 56.63 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3397 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGCCGAUGGGGGUGUUC GAACACCCCCAUCGGCGAC -2.4 -2.20 0.30 -1.00 0.00 5.00 -44.7 36.20 7.40 2.00 II 68.40 36.50 33.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3398 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCGCCGAUGGGGGUGUU AACACCCCCAUCGGCGACG -0.9 -2.40 -0.80 -1.00 -2.00 5.00 -44.7 23.70 -6.00 0.00 III 68.40 16.90 18.55 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3399 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGUCGCCGAUGGGGGUGU ACACCCCCAUCGGCGACGG -2.2 -3.30 -2.10 -1.00 -3.00 5.00 -47.1 25.20 -6.00 1.00 III 73.70 26.70 20.81 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3400 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGUCGCCGAUGGGGGUG CACCCCCAUCGGCGACGGC -2.1 -3.40 -2.50 0.00 0.00 5.00 -48.3 24.80 5.30 0.00 II 78.90 28.50 19.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3401 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCCGUCGCCGAUGGGGGU ACCCCCAUCGGCGACGGCC -2.2 -3.30 -3.00 1.00 -1.00 5.00 -49.5 19.30 -4.00 -2.00 III 78.90 18.30 36.26 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3402 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCCGUCGCCGAUGGGGG CCCCCAUCGGCGACGGCCC -3.3 -3.30 -3.80 3.00 2.00 6.00 -50.6 24.70 -2.60 -1.00 II 84.20 34.90 17.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3403 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGGCCGUCGCCGAUGGGG CCCCAUCGGCGACGGCCCC -3.3 -3.30 -3.80 1.00 1.00 7.00 -50.6 20.70 -4.70 -1.00 II 84.20 33.60 12.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3404 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGGGCCGUCGCCGAUGGG CCCAUCGGCGACGGCCCCG -3.3 -2.40 -3.80 -2.00 0.00 8.00 -49.7 13.70 -2.00 -2.00 II 84.20 25.80 3.78 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3405 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGGGGCCGUCGCCGAUGG CCAUCGGCGACGGCCCCGU -3.3 -2.20 -3.80 2.00 2.00 8.00 -48.6 25.30 0.10 1.00 II 78.90 42.40 10.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3406 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACGGGGCCGUCGCCGAUG CAUCGGCGACGGCCCCGUG -2.1 -2.10 -3.80 0.00 -1.00 8.00 -47.4 21.50 -4.40 0.00 II 78.90 43.30 33.38 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3407 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCACGGGGCCGUCGCCGAU AUCGGCGACGGCCCCGUGC -1.1 -3.40 -3.80 1.00 -1.00 8.00 -48.7 13.60 1.50 0.00 III 78.90 19.20 35.75 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3408 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCACGGGGCCGUCGCCGA UCGGCGACGGCCCCGUGCU -2.4 -2.10 -3.80 2.00 0.00 8.00 -49.7 27.70 -6.10 2.00 II 78.90 35.00 28.48 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3409 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCACGGGGCCGUCGCCG CGGCGACGGCCCCGUGCUG -2.4 -2.10 -3.80 1.00 2.00 8.00 -49.4 21.50 -1.70 1.00 II 84.20 45.60 35.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3410 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCAGCACGGGGCCGUCGCC GGCGACGGCCCCGUGCUGC -3.3 -3.40 -3.50 0.00 2.00 8.00 -50.4 15.00 7.50 -1.00 II 84.20 29.70 18.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3411 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCAGCACGGGGCCGUCGC GCGACGGCCCCGUGCUGCU -3.4 -2.10 -3.00 2.00 3.00 8.00 -49.2 37.90 9.80 2.00 II 78.90 49.10 42.04 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3412 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCAGCACGGGGCCGUCG CGACGGCCCCGUGCUGCUG -2.4 -2.10 -3.00 1.00 0.00 8.00 -47.9 26.60 0.70 1.00 II 78.90 43.90 40.44 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3413 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCAGCAGCACGGGGCCGUC GACGGCCCCGUGCUGCUGC -2.4 -3.40 -3.00 -1.00 1.00 8.00 -48.9 15.20 7.40 0.00 II 78.90 28.80 26.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3414 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCAGCAGCACGGGGCCGU ACGGCCCCGUGCUGCUGCC -2.2 -3.30 -3.00 0.00 -1.00 8.00 -49.8 19.40 -6.30 1.00 III 78.90 27.00 19.61 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3415 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCAGCAGCACGGGGCCG CGGCCCCGUGCUGCUGCCC -2.4 -3.30 -2.50 1.00 1.00 8.00 -50.9 8.70 2.70 -1.00 II 84.20 28.50 14.04 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3416 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGGCAGCAGCACGGGGCC GGCCCCGUGCUGCUGCCCG -3.3 -2.40 -1.70 -2.00 0.00 7.00 -50.9 15.50 5.50 -1.00 II 84.20 34.50 21.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3417 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGGGCAGCAGCACGGGGC GCCCCGUGCUGCUGCCCGA -3.4 -2.40 -0.60 1.00 3.00 6.00 -50 36.20 2.50 4.00 II 78.90 60.40 36.52 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3418 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCGGGCAGCAGCACGGGG CCCCGUGCUGCUGCCCGAC -3.3 -2.20 -0.60 1.00 2.00 5.00 -48.8 21.50 4.70 0.00 II 78.90 36.20 48.29 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3419 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUCGGGCAGCAGCACGGG CCCGUGCUGCUGCCCGACA -3.3 -2.10 -0.60 1.00 4.00 5.00 -47.6 27.80 -2.40 4.00 II 73.70 54.20 38.55 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3420 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUCGGGCAGCAGCACGG CCGUGCUGCUGCCCGACAA -3.3 -0.90 -0.60 0.00 4.00 5.00 -45.2 49.50 -4.90 6.00 II 68.40 67.70 77.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3421 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGUCGGGCAGCAGCACG CGUGCUGCUGCCCGACAAC -2.4 -2.20 -0.60 1.00 2.00 5.00 -44.1 43.00 4.70 3.00 II 68.40 48.20 79.88 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3422 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUUGUCGGGCAGCAGCAC GUGCUGCUGCCCGACAACC -2.2 -3.30 -0.60 1.00 1.00 5.00 -45 30.60 5.10 1.00 II 68.40 30.70 62.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3423 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGUUGUCGGGCAGCAGCA UGCUGCUGCCCGACAACCA -2.1 -2.10 -0.60 1.00 0.00 5.00 -44.9 46.80 -8.70 5.00 II 63.20 53.00 86.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3424 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGGUUGUCGGGCAGCAGC GCUGCUGCCCGACAACCAC -3.4 -2.20 -0.60 1.00 1.00 5.00 -45 46.50 9.80 2.00 II 68.40 50.90 72.87 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3425 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUGGUUGUCGGGCAGCAG CUGCUGCCCGACAACCACU -2.1 -2.10 2.00 2.00 3.00 5.00 -43.7 43.30 0.00 3.00 Ib 63.20 47.40 54.20 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3426 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UAGUGGUUGUCGGGCAGCA UGCUGCCCGACAACCACUA -2.1 -1.30 2.00 1.00 1.00 5.00 -42.9 47.30 -6.10 5.00 II 57.90 53.60 56.72 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3427 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUAGUGGUUGUCGGGCAGC GCUGCCCGACAACCACUAC -3.4 -2.20 2.00 -1.00 2.00 5.00 -43 35.70 5.10 3.00 II 63.20 49.80 50.43 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3428 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUAGUGGUUGUCGGGCAG CUGCCCGACAACCACUACC -2.1 -3.30 2.00 -1.00 1.00 5.00 -42.9 42.80 5.40 2.00 II 63.20 31.10 51.29 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3429 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGUAGUGGUUGUCGGGCA UGCCCGACAACCACUACCU -2.1 -2.10 2.10 3.00 0.00 5.00 -42.9 47.50 -1.10 4.00 II 57.90 44.00 61.02 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3430 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGUAGUGGUUGUCGGGC GCCCGACAACCACUACCUG -3.4 -2.10 3.00 0.00 2.00 5.00 -42.9 45.00 10.80 2.00 II 63.20 50.60 52.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3431 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCAGGUAGUGGUUGUCGGG CCCGACAACCACUACCUGA -3.3 -2.40 1.90 -1.00 4.00 4.00 -41.9 53.70 3.00 4.00 Ib 57.90 61.20 81.93 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3432 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCAGGUAGUGGUUGUCGG CCGACAACCACUACCUGAG -3.3 -2.10 1.90 1.00 2.00 3.00 -40.7 58.50 0.30 2.00 II 57.90 49.90 90.38 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3433 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUCAGGUAGUGGUUGUCG CGACAACCACUACCUGAGC -2.4 -3.40 1.90 1.00 2.00 2.00 -40.8 45.40 5.00 3.00 II 57.90 43.80 46.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3434 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCUCAGGUAGUGGUUGUC GACAACCACUACCUGAGCA -2.4 -2.10 1.90 -1.00 2.00 2.00 -40.5 61.40 10.40 6.00 II 52.60 52.90 52.40 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3435 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGCUCAGGUAGUGGUUGU ACAACCACUACCUGAGCAC -2.2 -2.20 1.90 1.00 -1.00 2.00 -40.3 53.80 -1.70 4.00 III 52.60 36.10 62.88 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3436 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUGCUCAGGUAGUGGUUG CAACCACUACCUGAGCACC -2.1 -3.30 1.90 1.00 1.00 2.00 -41.4 45.70 2.30 1.00 II 57.90 38.50 40.65 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3437 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUGCUCAGGUAGUGGUU AACCACUACCUGAGCACCC -0.9 -3.30 1.90 0.00 -2.00 3.00 -42.6 45.70 -3.50 1.00 III 57.90 27.60 79.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3438 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGGUGCUCAGGUAGUGGU ACCACUACCUGAGCACCCA -2.2 -2.10 1.90 1.00 1.00 3.00 -43.8 58.00 -4.00 4.00 II 57.90 54.10 97.99 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3439 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUGGGUGCUCAGGUAGUGG CCACUACCUGAGCACCCAG -3.3 -2.10 -0.60 -1.00 1.00 3.00 -43.7 44.80 2.60 2.00 II 63.20 49.20 75.84 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3440 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUGGGUGCUCAGGUAGUG CACUACCUGAGCACCCAGU -2.1 -2.20 -1.20 2.00 3.00 3.00 -42.6 36.80 -2.40 2.00 II 57.90 46.50 51.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3441 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GACUGGGUGCUCAGGUAGU ACUACCUGAGCACCCAGUC -2.2 -2.40 -1.20 0.00 -1.00 3.00 -42.9 38.40 -8.90 1.00 III 57.90 34.10 36.88 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3442 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGACUGGGUGCUCAGGUAG CUACCUGAGCACCCAGUCC -2.1 -3.30 -1.20 1.00 0.00 3.00 -44 40.00 3.10 2.00 II 63.20 37.40 67.08 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3443 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGACUGGGUGCUCAGGUA UACCUGAGCACCCAGUCCG -1.3 -2.40 -1.20 0.00 -4.00 3.00 -44.3 39.70 -8.10 0.00 III 63.20 26.60 64.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3444 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGACUGGGUGCUCAGGU ACCUGAGCACCCAGUCCGC -2.2 -3.40 -1.20 2.00 0.00 4.00 -46.4 32.50 3.50 0.00 III 68.40 33.90 69.96 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3445 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCGGACUGGGUGCUCAGG CCUGAGCACCCAGUCCGCC -3.3 -3.30 -1.20 1.00 0.00 5.00 -47.5 27.70 3.00 -2.00 II 73.70 28.50 40.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3446 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGCGGACUGGGUGCUCAG CUGAGCACCCAGUCCGCCC -2.1 -3.30 -0.90 0.00 0.00 6.00 -47.5 25.80 0.00 0.00 II 73.70 30.20 41.95 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3447 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGGCGGACUGGGUGCUCA UGAGCACCCAGUCCGCCCU -2.1 -2.10 0.50 2.00 0.00 6.00 -47.5 36.20 -1.40 3.00 II 68.40 40.10 49.79 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3448 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGGCGGACUGGGUGCUC GAGCACCCAGUCCGCCCUG -2.4 -2.10 -0.10 -2.00 0.00 6.00 -47.5 21.00 5.40 1.00 II 73.70 38.00 44.88 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3449 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCAGGGCGGACUGGGUGCU AGCACCCAGUCCGCCCUGA -2.1 -2.40 -1.20 0.00 2.00 6.00 -47.5 30.00 -3.30 3.00 II 68.40 47.10 43.21 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3450 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCAGGGCGGACUGGGUGC GCACCCAGUCCGCCCUGAG -3.4 -2.10 -1.20 -1.00 0.00 6.00 -47.5 37.30 5.40 2.00 II 73.70 45.50 64.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3451 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUCAGGGCGGACUGGGUG CACCCAGUCCGCCCUGAGC -2.1 -3.40 -1.20 2.00 2.00 6.00 -47.5 28.50 7.40 1.00 II 73.70 34.50 51.63 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3452 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCUCAGGGCGGACUGGGU ACCCAGUCCGCCCUGAGCA -2.2 -2.10 -1.20 1.00 1.00 6.00 -47.5 41.80 -6.60 3.00 II 68.40 43.30 51.85 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3453 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGCUCAGGGCGGACUGGG CCCAGUCCGCCCUGAGCAA -3.3 -0.90 -1.20 2.00 4.00 6.00 -46.2 43.10 -2.40 4.00 Ib 68.40 64.40 34.08 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3454 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUUGCUCAGGGCGGACUGG CCAGUCCGCCCUGAGCAAA -3.3 -0.90 -1.20 0.00 4.00 6.00 -43.8 49.10 -2.40 4.00 Ib 63.20 60.00 73.77 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3455 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUUGCUCAGGGCGGACUG CAGUCCGCCCUGAGCAAAG -2.1 -2.10 -0.90 -1.00 1.00 6.00 -42.6 51.90 0.40 3.00 II 63.20 46.20 77.81 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3456 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCUUUGCUCAGGGCGGACU AGUCCGCCCUGAGCAAAGA -2.1 -2.40 -0.80 1.00 1.00 6.00 -42.9 61.90 -4.00 6.00 II 57.90 56.20 83.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3457 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCUUUGCUCAGGGCGGAC GUCCGCCCUGAGCAAAGAC -2.2 -2.20 -0.80 -1.00 1.00 6.00 -43 46.00 9.70 3.00 II 63.20 38.40 80.58 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3458 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCUUUGCUCAGGGCGGA UCCGCCCUGAGCAAAGACC -2.4 -3.30 -0.80 2.00 -1.00 6.00 -44.1 32.90 -6.10 2.00 II 63.20 25.90 54.93 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3459 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGUCUUUGCUCAGGGCGG CCGCCCUGAGCAAAGACCC -3.3 -3.30 -0.80 1.00 1.00 6.00 -45 41.70 -4.90 1.00 II 68.40 40.30 44.99 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3460 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGGGUCUUUGCUCAGGGCG CGCCCUGAGCAAAGACCCC -2.4 -3.30 -0.80 1.00 1.00 5.00 -45 46.90 3.10 1.00 II 68.40 44.70 59.56 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3461 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGGGGUCUUUGCUCAGGGC GCCCUGAGCAAAGACCCCA -3.4 -2.10 -0.50 0.00 3.00 4.00 -44.7 53.00 5.10 2.00 II 63.20 56.50 52.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3462 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGGGGUCUUUGCUCAGGG CCCUGAGCAAAGACCCCAA -3.3 -0.90 0.50 1.00 5.00 4.00 -42.2 58.60 4.70 4.00 II 57.90 70.90 80.40 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3463 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUUGGGGUCUUUGCUCAGG CCUGAGCAAAGACCCCAAC -3.3 -2.20 0.50 1.00 2.00 4.00 -41.1 47.60 3.00 2.00 II 57.90 47.70 58.79 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3464 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUUGGGGUCUUUGCUCAG CUGAGCAAAGACCCCAACG -2.1 -2.40 0.80 -2.00 0.00 4.00 -40.2 46.40 1.00 2.00 II 57.90 37.20 50.17 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3465 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGUUGGGGUCUUUGCUCA UGAGCAAAGACCCCAACGA -2.1 -2.40 2.70 1.00 0.00 4.00 -40.5 65.10 -0.80 7.00 II 52.60 53.10 81.08 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3466 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGUUGGGGUCUUUGCUC GAGCAAAGACCCCAACGAG -2.4 -2.10 0.00 1.00 4.00 -40.5 56.50 5.40 2.00 II 57.90 53.40 79.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3467 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCUCGUUGGGGUCUUUGCU AGCAAAGACCCCAACGAGA -2.1 -2.40 3.00 3.00 4.00 -40.5 68.70 3.80 5.00 II 52.60 57.90 82.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3468 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUCUCGUUGGGGUCUUUGC GCAAAGACCCCAACGAGAA -3.4 -0.90 2.00 3.00 4.00 -39.3 82.90 7.40 7.00 Ib 52.60 70.20 92.10 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3469 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUCUCGUUGGGGUCUUUG CAAAGACCCCAACGAGAAG -2.1 -2.10 0.00 1.00 4.00 -38 64.50 0.30 5.00 II 52.60 51.40 71.51 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3470 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUUCUCGUUGGGGUCUUU AAAGACCCCAACGAGAAGC -0.9 -3.40 -1.00 -2.00 4.00 -39.3 48.80 -4.00 3.00 III 52.60 23.00 14.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3471 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCUUCUCGUUGGGGUCUU AAGACCCCAACGAGAAGCG -0.9 -2.40 1.40 0.00 -3.00 4.00 -40.8 44.20 -6.00 2.00 III 57.90 29.10 11.33 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3472 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGCUUCUCGUUGGGGUCU AGACCCCAACGAGAAGCGC -2.1 -3.40 1.00 1.00 -2.00 4.00 -43.3 39.70 -1.00 1.00 III 63.20 31.50 17.22 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3473 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGCGCUUCUCGUUGGGGUC GACCCCAACGAGAAGCGCG -2.4 -2.40 1.00 -1.00 -1.00 5.00 -43.6 49.30 8.40 0.00 II 68.40 38.10 31.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3474 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGCGCUUCUCGUUGGGGU ACCCCAACGAGAAGCGCGA -2.2 -2.40 0.60 3.00 2.00 5.00 -43.6 55.20 -4.00 3.00 II 63.20 51.00 84.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3475 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUCGCGCUUCUCGUUGGGG CCCCAACGAGAAGCGCGAU -3.3 -1.10 0.60 1.00 5.00 5.00 -42.5 48.20 0.00 2.00 II 63.20 53.50 84.64 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3476 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUCGCGCUUCUCGUUGGG CCCAACGAGAAGCGCGAUC -3.3 -2.40 0.60 0.00 3.00 5.00 -41.6 43.80 3.10 2.00 II 63.20 36.90 74.41 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3477 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAUCGCGCUUCUCGUUGG CCAACGAGAAGCGCGAUCA -3.3 -2.10 0.60 1.00 3.00 5.00 -40.4 63.80 -2.40 5.00 II 57.90 60.10 83.93 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3478 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGAUCGCGCUUCUCGUUG CAACGAGAAGCGCGAUCAC -2.1 -2.20 0.60 1.00 1.00 5.00 -39.3 61.10 7.80 4.00 II 57.90 49.60 78.72 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3479 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUGAUCGCGCUUCUCGUU AACGAGAAGCGCGAUCACA -0.9 -2.10 0.60 1.00 1.00 5.00 -39.3 62.30 -0.60 5.00 II 52.60 52.20 77.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3480 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGUGAUCGCGCUUCUCGU ACGAGAAGCGCGAUCACAU -2.2 -1.10 0.60 3.00 3.00 5.00 -39.5 65.80 -4.00 5.00 II 52.60 55.10 83.23 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3481 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAUGUGAUCGCGCUUCUCG CGAGAAGCGCGAUCACAUG -2.4 -2.10 0.90 0.00 2.00 5.00 -39.4 62.70 0.40 4.00 II 57.90 58.50 82.60 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3482 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAUGUGAUCGCGCUUCUC GAGAAGCGCGAUCACAUGG -2.4 -3.30 1.20 -1.00 0.00 5.00 -40.3 46.90 3.10 2.00 II 57.90 43.90 58.75 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3483 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACCAUGUGAUCGCGCUUCU AGAAGCGCGAUCACAUGGU -2.1 -2.20 1.00 1.00 0.00 5.00 -40.1 54.90 -3.90 6.00 II 52.60 45.30 47.59 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3484 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GACCAUGUGAUCGCGCUUC GAAGCGCGAUCACAUGGUC -2.4 -2.40 -1.80 2.00 0.00 5.00 -40.4 50.10 7.80 3.00 II 57.90 49.20 61.12 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3485 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGACCAUGUGAUCGCGCUU AAGCGCGAUCACAUGGUCC -0.9 -3.30 -2.60 1.00 -1.00 5.00 -41.3 42.60 3.80 0.00 III 57.90 30.90 43.28 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3486 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGGACCAUGUGAUCGCGCU AGCGCGAUCACAUGGUCCU -2.1 -2.10 -2.60 2.00 1.00 5.00 -42.5 56.50 -4.00 2.00 II 57.90 48.20 61.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3487 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGGACCAUGUGAUCGCGC GCGCGAUCACAUGGUCCUG -3.4 -2.10 -2.60 -1.00 2.00 5.00 -42.5 41.00 7.80 0.00 II 63.20 50.70 47.42 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3488 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCAGGACCAUGUGAUCGCG CGCGAUCACAUGGUCCUGC -2.4 -3.40 -2.60 0.00 2.00 4.00 -42.5 32.30 3.00 -1.00 II 63.20 34.60 29.11 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3489 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCAGGACCAUGUGAUCGC GCGAUCACAUGGUCCUGCU -3.4 -2.10 -2.60 1.00 3.00 3.00 -42.2 50.10 7.40 3.00 II 57.90 56.30 38.65 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3490 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCAGGACCAUGUGAUCG CGAUCACAUGGUCCUGCUG -2.4 -2.10 -2.60 1.00 1.00 2.00 -40.9 52.90 8.40 2.00 II 57.90 53.40 50.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 45-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3491 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAGCAGGACCAUGUGAUC GAUCACAUGGUCCUGCUGG -2.4 -3.30 -2.30 -2.00 -1.00 2.00 -41.8 36.60 3.10 0.00 II 57.90 36.50 62.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 46-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3492 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCAGCAGGACCAUGUGAU AUCACAUGGUCCUGCUGGA -1.1 -2.40 -1.80 1.00 1.00 2.00 -41.8 57.00 -8.90 5.00 II 52.60 50.80 76.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 47-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3493 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCCAGCAGGACCAUGUGA UCACAUGGUCCUGCUGGAG -2.4 -2.10 -2.60 1.00 -3.00 2.00 -42.8 39.50 -0.70 1.00 III 57.90 33.70 36.24 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 48-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3494 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUCCAGCAGGACCAUGUG CACAUGGUCCUGCUGGAGU -2.1 -2.20 -2.60 2.00 3.00 2.00 -42.6 46.00 2.40 2.00 II 57.90 45.40 78.82 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 49-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3495 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AACUCCAGCAGGACCAUGU ACAUGGUCCUGCUGGAGUU -2.2 -0.90 -2.60 2.00 1.00 2.00 -41.4 68.00 -6.60 6.00 II 52.60 57.20 56.39 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 50-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3496 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAACUCCAGCAGGACCAUG CAUGGUCCUGCUGGAGUUC -2.1 -2.40 -2.60 2.00 1.00 2.00 -41.6 42.10 2.30 1.00 II 57.90 42.60 71.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 51-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3497 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAACUCCAGCAGGACCAU AUGGUCCUGCUGGAGUUCG -1.1 -2.40 -2.60 -2.00 -2.00 2.00 -41.9 33.30 -8.30 0.00 III 57.90 27.30 30.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 52-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3498 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACGAACUCCAGCAGGACCA UGGUCCUGCUGGAGUUCGU -2.1 -2.20 -2.60 2.00 0.00 2.00 -43 49.10 -6.00 4.00 II 57.90 49.70 86.15 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 53-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3499 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CACGAACUCCAGCAGGACC GGUCCUGCUGGAGUUCGUG -3.3 -2.10 -2.60 0.00 0.00 2.00 -43 45.50 12.80 0.00 II 63.20 46.70 74.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 54-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3500 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCACGAACUCCAGCAGGAC GUCCUGCUGGAGUUCGUGA -2.2 -2.40 -2.60 1.00 3.00 2.00 -42.1 38.60 5.10 3.00 Ib 57.90 54.00 44.11 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 55-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3501 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCACGAACUCCAGCAGGA UCCUGCUGGAGUUCGUGAC -2.4 -2.20 -2.40 0.00 -1.00 2.00 -42.1 39.10 -11.00 1.00 III 57.90 34.50 85.24 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 56-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3502 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGUCACGAACUCCAGCAGG CCUGCUGGAGUUCGUGACC -3.3 -3.30 -0.80 1.00 1.00 2.00 -43 37.20 2.80 2.00 II 63.20 39.60 52.67 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 57-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3503 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGUCACGAACUCCAGCAG CUGCUGGAGUUCGUGACCG -2.1 -2.40 0.30 -1.00 -1.00 3.00 -42.1 45.20 1.10 1.00 II 63.20 32.00 75.73 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 58-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3504 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGUCACGAACUCCAGCA UGCUGGAGUUCGUGACCGC -2.1 -3.40 0.30 1.00 -2.00 4.00 -43.4 45.10 -3.80 2.00 III 63.20 37.80 36.89 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 59-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3505 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCGGUCACGAACUCCAGC GCUGGAGUUCGUGACCGCC -3.4 -3.30 0.30 1.00 1.00 5.00 -44.6 39.10 14.40 -1.00 II 68.40 39.50 30.95 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 60-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3506 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGCGGUCACGAACUCCAG CUGGAGUUCGUGACCGCCG -2.1 -2.40 0.30 1.00 -1.00 6.00 -43.6 31.70 -4.60 0.00 II 68.40 36.70 39.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 61-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3507 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCGGCGGUCACGAACUCCA UGGAGUUCGUGACCGCCGC -2.1 -3.40 -0.10 1.00 -2.00 7.00 -44.9 30.00 -8.70 1.00 III 68.40 35.10 32.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 62-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3508 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GGCGGCGGUCACGAACUCC GGAGUUCGUGACCGCCGCC -3.3 -3.30 -0.90 0.00 0.00 8.00 -46.1 26.40 7.40 1.00 II 73.70 38.20 40.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 63-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3509 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGGCGGCGGUCACGAACUC GAGUUCGUGACCGCCGCCG -2.4 -2.40 -0.90 0.00 -1.00 9.00 -45.2 13.50 5.50 -1.00 II 73.70 28.60 28.30 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 64-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3510 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGGCGGCGGUCACGAACU AGUUCGUGACCGCCGCCGG -2.1 -3.30 -1.30 0.00 -3.00 10.00 -46.1 23.50 -10.90 -1.00 III 73.70 38.20 30.00 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 10-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3511 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCCGGCGGCGGUCACGAAC GUUCGUGACCGCCGCCGGG -2.2 -3.30 -2.60 0.00 -2.00 11.00 -47.3 26.80 10.80 -1.00 II 78.90 33.10 33.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 11-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3512 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCCGGCGGCGGUCACGAA UUCGUGACCGCCGCCGGGA -0.9 -2.40 -2.60 2.00 -1.00 11.00 -47.5 24.80 -3.80 1.00 II 73.70 29.80 29.13 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 12-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3513 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUCCCGGCGGCGGUCACGA UCGUGACCGCCGCCGGGAU -2.4 -1.10 -2.60 3.00 2.00 11.00 -47.7 30.60 -3.80 2.00 II 73.70 43.90 34.74 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 13-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3514 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAUCCCGGCGGCGGUCACG CGUGACCGCCGCCGGGAUC -2.4 -2.40 -2.60 1.00 2.00 11.00 -47.7 29.20 -2.40 1.00 II 78.90 39.20 25.27 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 14-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3515 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGAUCCCGGCGGCGGUCAC GUGACCGCCGCCGGGAUCA -2.2 -2.10 -2.60 0.00 3.00 11.00 -47.4 42.50 9.80 3.00 II 73.70 44.60 69.59 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 15-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3516 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUGAUCCCGGCGGCGGUCA UGACCGCCGCCGGGAUCAC -2.1 -2.20 -2.60 1.00 -2.00 11.00 -47.4 33.60 -6.10 2.00 III 73.70 32.30 14.39 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 16-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3517 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGUGAUCCCGGCGGCGGUC GACCGCCGCCGGGAUCACU -2.4 -2.10 -2.60 1.00 3.00 11.00 -47.4 32.00 7.80 2.00 Ib 73.70 45.10 30.53 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 17-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3518 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAGUGAUCCCGGCGGCGGU ACCGCCGCCGGGAUCACUC -2.2 -2.40 -2.60 1.00 0.00 11.00 -47.4 32.30 -1.60 1.00 II 73.70 30.20 57.62 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 18-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3519 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGAGUGAUCCCGGCGGCGG CCGCCGCCGGGAUCACUCU -3.3 -2.10 -2.10 2.00 4.00 11.00 -47.3 35.00 -2.40 3.00 Ib 73.70 54.30 26.93 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 19-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3520 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GAGAGUGAUCCCGGCGGCG CGCCGCCGGGAUCACUCUC -2.4 -2.40 -1.00 -1.00 2.00 10.00 -46.4 26.80 -4.70 1.00 II 73.70 42.70 32.57 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 20-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3521 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGAGAGUGAUCCCGGCGGC GCCGCCGGGAUCACUCUCG -3.4 -2.40 -3.40 -1.00 1.00 9.00 -46.4 25.20 5.80 1.00 II 73.70 38.90 47.36 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 21-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3522 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCGAGAGUGAUCCCGGCGG CCGCCGGGAUCACUCUCGG -3.3 -3.30 -6.60 0.00 0.00 8.00 -46.3 30.70 -2.00 1.00 II 73.70 42.60 29.72 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 22-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3523 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCCGAGAGUGAUCCCGGCG CGCCGGGAUCACUCUCGGC -2.4 -3.40 -10.10 0.00 1.00 7.00 -46.4 32.10 10.40 0.00 II 73.70 40.30 31.46 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 23-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3524 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGCCGAGAGUGAUCCCGGC GCCGGGAUCACUCUCGGCA -3.4 -2.10 -11.50 2.00 3.00 6.00 -46.1 38.80 7.40 2.00 II 68.40 53.10 15.45 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 24-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3525 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AUGCCGAGAGUGAUCCCGG CCGGGAUCACUCUCGGCAU -3.3 -1.10 -6.80 2.00 5.00 5.00 -43.8 45.60 -0.30 2.00 II 63.20 63.20 25.13 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 25-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3526 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAUGCCGAGAGUGAUCCCG CGGGAUCACUCUCGGCAUG -2.4 -2.10 -4.40 0.00 2.00 4.00 -42.6 49.70 1.00 2.00 II 63.20 52.90 31.76 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 26-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3527 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CCAUGCCGAGAGUGAUCCC GGGAUCACUCUCGGCAUGG -3.3 -3.30 -2.40 -2.00 1.00 4.00 -43.5 41.40 7.70 0.00 II 63.20 39.50 24.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 27-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3528 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCCAUGCCGAGAGUGAUCC GGAUCACUCUCGGCAUGGA -3.3 -2.40 1.00 1.00 3.00 4.00 -42.6 62.30 9.70 6.00 II 57.90 65.60 62.83 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 28-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3529 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUCCAUGCCGAGAGUGAUC GAUCACUCUCGGCAUGGAC -2.4 -2.20 0.80 1.00 0.00 4.00 -41.5 45.60 9.80 2.00 II 57.90 44.00 26.06 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 29-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3530 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CGUCCAUGCCGAGAGUGAU AUCACUCUCGGCAUGGACG -1.1 -2.40 0.80 2.00 -2.00 4.00 -41.5 40.60 -6.00 1.00 III 57.90 28.00 21.86 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 30-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3531 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UCGUCCAUGCCGAGAGUGA UCACUCUCGGCAUGGACGA -2.4 -2.40 -0.90 0.00 -1.00 4.00 -42.8 48.20 -8.70 5.00 II 57.90 44.60 11.37 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 31-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3532 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUCGUCCAUGCCGAGAGUG CACUCUCGGCAUGGACGAG -2.1 -2.10 -3.50 -1.00 0.00 4.00 -42.5 38.90 -6.70 0.00 II 63.20 43.50 25.11 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 32-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3533 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GCUCGUCCAUGCCGAGAGU ACUCUCGGCAUGGACGAGC -2.2 -3.40 -3.90 0.00 -1.00 4.00 -43.8 32.10 -3.90 -1.00 III 63.20 21.50 9.14 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 33-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3534 NZ_CP024869 Takayuki Katoh EGFP 2315885245 AGCUCGUCCAUGCCGAGAG CUCUCGGCAUGGACGAGCU -2.1 -2.10 -3.90 3.00 2.00 4.00 -43.7 56.60 2.40 3.00 II 63.20 51.30 60.36 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 34-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3535 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CAGCUCGUCCAUGCCGAGA UCUCGGCAUGGACGAGCUG -2.4 -2.10 -3.90 1.00 -3.00 4.00 -43.7 45.90 -0.40 1.00 III 63.20 37.10 83.09 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 35-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3536 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACAGCUCGUCCAUGCCGAG CUCGGCAUGGACGAGCUGU -2.1 -2.20 -3.80 0.00 3.00 4.00 -43.5 37.70 -2.40 1.00 II 63.20 42.60 33.35 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 36-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3537 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UACAGCUCGUCCAUGCCGA UCGGCAUGGACGAGCUGUA -2.4 -1.30 -3.50 2.00 2.00 4.00 -42.7 57.50 -8.70 4.00 II 57.90 56.70 66.79 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 37-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3538 NZ_CP024869 Takayuki Katoh EGFP 2315885245 GUACAGCUCGUCCAUGCCG CGGCAUGGACGAGCUGUAC -2.4 -2.20 -3.40 2.00 3.00 4.00 -42.5 41.10 2.80 1.00 II 63.20 51.50 56.75 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 38-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3539 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UGUACAGCUCGUCCAUGCC GGCAUGGACGAGCUGUACA -3.3 -2.10 -1.60 0.00 4.00 3.00 -42.2 66.00 12.80 4.00 Ib 57.90 62.40 73.66 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 39-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3540 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUGUACAGCUCGUCCAUGC GCAUGGACGAGCUGUACAA -3.4 -0.90 -0.50 1.00 3.00 2.00 -39.8 73.70 7.80 8.00 Ia 52.60 72.50 76.68 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 40-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3541 NZ_CP024869 Takayuki Katoh EGFP 2315885245 CUUGUACAGCUCGUCCAUG CAUGGACGAGCUGUACAAG -2.1 -2.10 0.60 0.00 1.00 2.00 -38.5 49.50 -2.00 3.00 II 52.60 48.00 53.54 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 41-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3542 NZ_CP024869 Takayuki Katoh EGFP 2315885245 ACUUGUACAGCUCGUCCAU AUGGACGAGCUGUACAAGU -1.1 -2.20 -0.20 0.00 1.00 2.00 -38.6 59.40 -0.90 5.00 II 47.40 42.20 68.43 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 42-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3543 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UACUUGUACAGCUCGUCCA UGGACGAGCUGUACAAGUA -2.1 -1.30 -0.90 2.00 1.00 2.00 -38.8 80.60 -6.10 8.00 II 47.40 66.20 82.90 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 43-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26 Si3544 NZ_CP024869 Takayuki Katoh EGFP 2315885245 UUACUUGUACAGCUCGUCC GGACGAGCUGUACAAGUAA -3.3 -0.90 -0.90 1.00 5.00 2.00 -37.6 82.80 14.40 8.00 Ia 47.40 79.60 83.47 Flow cytometry and immunofluorescence HeLa 150nM 72h "Specific residues at every third position of siRNA shape its efficient RNAi activity. shape its efficient RNAi activity" 17259216 2007 Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm (‘siExplorer’) developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 44-nt periodicity provides a new aspect unveiling siRNA functionality. Nucleic Acids Research 2007/1/26